Effect of age at thyroid stimulating hormone normalization on postural control in children with congenital hypothyroidism

Neonatal screening programmes allow early treatment to limit the consequences of congenital hypothyroidism on maturation of the central nervous system, and on psychomotor and educational outcome. Consequences of age at thyroid stimulating hormone (TSH) normalization on postural control were evaluated in 17 children with congenital hypothyroidism (14 females, three males; median age 12 years 1 month, range 7 to 14 years) and in 11 control individuals (eight females, three males: median age 10 years 6 months, range 8 to 14 years). Children with congenital hypothyroidism were split into two groups according to time of TSH normalization: before (group 1) or after (group 2) 3 months of age. Posturography (static and dynamic tests), educational (school performance), and psychomotor (WISC and revised Bruininks Oseretsky tests) evaluations were carried out. Group 2 results showed significant abnormalities in postural, educational, and psychomotor aptitudes in comparison with group 1 and control children (stability, Bruininks-Oseretsky, school performance: p < or = 0.05 or p < or = 0.01). Early TSH normalization is necessary to allow for normal development of the neurosensorial afferent pathways (vestibular, proprioceptive) and of central integration (cerebellum, vestibular nuclei).     

Accuracy of episodic autobiographical memory in children with early thyroid hormone deficiency using a staged event

Autobiographical memory (AM) is a highly constructive cognitive process that often contains memory errors. No study has specifically examined AM accuracy in children with abnormal development of the hippocampus, a crucial brain region for AM retrieval. Thus, the present study investigated AM accuracy in 68 typically and atypically developing children using a staged autobiographical event, the Children's Autobiographical Interview, and structural magnetic resonance imaging. The atypically developing group consisted of 17 children (HYPO) exposed during gestation to insufficient maternal thyroid hormone (TH), a critical substrate for hippocampal development, and 25 children with congenital hypothyroidism (CH), who were compared to 26 controls. Groups differed significantly in the number of accurate episodic details recalled and proportion accuracy scores, with controls having more accurate recollections of the staged event than both TH-deficient groups. Total hippocampal volumes and anterior hippocampal volumes were positively correlated with proportion accuracy scores, but not total accurate episodic details, in HYPO and CH. In addition, greater severity of TH deficiency predicted lower proportion accuracy scores in both HYPO and CH. Overall, these results indicate that children with early TH deficiency have deficits in AM accuracy and that the anterior hippocampus may play a particularly important role in accurate AM retrieval.     

Subclinical hypothyroidism during valproic acid therapy in children and adolescents with epilepsy

The aim of this study was to evaluate the incidence of thyroid dysfunction during valproic acid (VPA) therapy in children and adolescents with epilepsy. The serum levels of thyroid-stimulating hormone (TSH), free thyroxine, and triiodothyronine were evaluated in 61 children with epilepsy who received VPA monotherapy for more than 6 months and in 144 controls. We analyzed the effect of age, seizure type, duration of VPA treatment, dose of VPA, and serum level of VPA on thyroid function. The incidence of subclinical hypothyroidism was significantly higher in patients with VPA therapy than in controls (52.4 vs. 16.7%; p < 0.001). In addition, of the 61 patients, 5 (8.1%) exhibited TSH levels that were >10 μIU/mL. However, none of the patients and controls showed overt hypothyroidism. Serum VPA level and daily dose of VPA were correlated with TSH level. Subclinical hypothyroidism developed frequently in children and adolescents during VPA therapy.     

Developmental Iodine Deficiency and Hypothyroidism Impair Spatial Memory in Adolescent Rat Hippocampus: Involvement of CaMKII, Calmodulin and Calcineurin

Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal calcium/calmodulin-dependent protein kinase II (CaMKII), calmodulin and calcineurin are implicated in the impaired spatial memory in adolescent rats following developmental ID and hypothyroidism. Three developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 28. Then, the spatial memory to a water maze test was studied in pups before PN42. After testing periods, the latency to platform and the number of error in iodine-deficient and 15 ppm PTU-treatment groups were significantly higher than those in the controls (P < 0.05). Total and phosphorylated CaMKII, calmodulin, and calcineurin in the hippocampus were detected with both the immunohistochemistry and western blotting. Without going through water maze test, iodine-deficient and 15 ppm PTU-treatment groups showed significantly lower CaMKII and calmodulin and significantly higher calcineurin than the controls in hippocampal CA1 and CA3 regions (P < 0.05). After trials of water maze task, however, CaMKII and calmodulin were up-regulated and calcineurin was down-regulated in control group (P < 0.05), but not in iodine-deficient and 15 ppm PTU-treatment groups. Data indicate that hippocampal CaMKII, calmodulin, and calcineurin are involved in the impaired spatial memory induced by developmental ID and hypothyroidism.     

Hypothyroidism

Thyroid function is essential to growth and to all aspects of development. Hypothyroidism is not preventable, however, early detection and immediate treatment can prevent deleterious and irreversible effects on the growing child. Newborn screening is mandated in all fifty states and it is critical to the early detection of congenital hypothyroidism and the institution of treatment in the first weeks of life. Awareness of acquired hypothyroidism in school-aged children and adolescents is important to the detection of this often subtle condition that usually first presents as deceleration of growth. Lymphocytic thyroiditis is the most common cause of acquired thyroid deficiency in children and adolescents. Hypothyroidism may also develop years after radiation treatment for cancer directed at the area of the thyroid gland or the cranium. Replacement therapy with thyroxine is generally well tolerated. The use of lithium carbonate and other medications, as well as conditions of starvation and chronic malnutrition may be associated with disturbed thyroid function. Persons with the rare disorder of generalized resistance to thyroid hormone are at significant risk for attention deficit hyperactivity disorder. However, the reverse is not the case.     

Attention problems in adolescents with congenital hypothyroidism: a multicomponential analysis.

Even though early treatment of congenital hypothyroidism (CH) with newborn screening prevents the mental retardation previously seen in cretinism, affected children still exhibit subtle persisting neurocognitive deficits. One of their commonest problems is poor attention, which reflects both early disease severity and later (high) circulating thyroid hormone levels. While attention is currently regarded as multicomponential in nature, with different processing components supported by different brain regions, the specific components of attention affected by CH have not been identified. In light of animal evidence showing that neonatal thyroid hormone deficiencies impede the neurodevelopment of structures important for selective aspects of attention, we proposed a multicomponential approach to study attention in children with CH. This was accomplished via retrospective analysis of existing data on adolescents with CH whose attention was previously evaluated using multiple tests. Results showed significantly poorer overall attention in CH than controls with differences occurring mainly on focus and inhibit indices. However, performance on various indices was associated with different disease parameters. Poor encode and focus were correlated with more severe hypothyroidism and a longer period of thyroid hormone insufficiency and poor select and shift with higher thyroid hormone levels at testing. These results signify that thyroid hormone is important for the development and later regulation of brain structures supporting distinct aspects of attention.     

Adult-onset hypothyroidism impairs paired-pulse facilitation and long-term potentiation of the rat dorsal hippocampo-medial prefrontal cortex pathway in vivo

Thyroid hormones are critical for the maturation and function of the central nervous system. Insufficiency of thyroid hormones in the adulthood causes a wide range of cognitive dysfunctions, including deficits in learning and memory. The present study investigated whether adult-onset hypothyroidism would alter synaptic functions in the dorsal hippocampo-medial prefrontal cortex (mPFC) pathway, a neural pathway important for learning and memory. Adult hypothyroidism was induced by oral administration of 1% (g/l) antithyroid acting drug 6-n-propyl-2-thiouracil (PTU) to adult male Sprague-Dawley rats for 4 weeks. Postsynaptic potentials (PSP) were recorded in the mPFC by stimulating the dorsal hippocampal CA1 region in vivo. Basal synaptic transmission was evaluated by comparing input-output relationships. Paired-pulse facilitation and long-term potentiation were recorded to examine short- and long-term synaptic plasticity. Adult-onset hypothyroidism did not change the basal synaptic transmission, but significantly reduced paired-pulse facilitation and long-term potentiation of PSP. These inhibitions can be restored by thyroid hormone replacement. The results suggest that such alterations in synaptic plasticity of the dorsal hippocampo-mPFC pathway might contribute to understanding basic mechanisms underlying learning and memory deficits associated with adult-onset hypothyroidism.     

Word and face recognition in children with congenital hypothyroidism: an event-related potential study

The repetition paradigm offers a useful technique for assessing recognition memory by evaluating how an individual responds to new versus old stimuli. While this paradigm has been extensively used in adults with and without clinical conditions, it has not, to our knowledge, been studied in a clinical pediatric population. Children with congenital hypothyroidism (CH) identified by newborn screening and treated early in life have normal intelligence but demonstrate residual cognitive deficits including selective memory problems that are attributed to their loss of thyroid hormone during hippocampal formation. Since the hippocampus is integral for recognition memory, we hypothesized that children with CH would perform atypically on the repetition paradigm. Event-related potentials (ERPs) were recorded during word and face recognition in nine children aged 11 to 13 years with CH and nine typically developing children matched for age. Results revealed that while the groups did not differ in accuracy or reaction time, they did differ significantly on selective ERP components. Like normal adults, the comparison children showed a positive elevation in P3 amplitude for repeated relative to new words at the parietal electrodes, whereas children with CH did not. Both groups produced weak repetition effects when viewing faces, although the amplitudes of children with CH were somewhat smaller. It is proposed that the dampened neurophysiological response to repeated verbal stimuli by children with CH may explain some of their clinically observed difficulties in short-term recognition memory.     

Age-related changes in regional activation during working memory in young adults: an fMRI study.

Several lines of evidence suggest that working memory diminishes with advancing age, with concomitant functional changes in associated neuronal activation in frontal cortical regions and hippocampi. No studies to date, however, have investigated age-related changes in neuronal activation in these regions during performance of a working memory task in younger subjects without working memory deficits. In this study, we utilized fMRI to examine changes in brain activation with increasing age in specific regions-of-interest. Eleven healthy subjects performed a "two-back" working memory task and a matched "zero-back" attention task during fMRI. There was no association between age and performance on either task. Left hippocampal activation significantly correlated with age (P = 0.01) and right hippocampal activation showed an association with age (P = 0.09). This study demonstrates that increasing age is associated with increased activation of hippocampus even in young patients without evidence of working memory deficits and suggests that functional changes may precede overt evidence of working memory deficits.     

A cross-sectional and follow-up functional MRI study with a working memory task in adolescent anorexia nervosa

Structural and functional brain abnormalities have been described in anorexia nervosa (AN). The objective of this study was to examine whether there is abnormal regional brain activation during a working memory task not associated with any emotional stimuli in adolescent patients with anorexia and to detect possible changes after weight recovery. Fourteen children and adolescents (age range 11–18 years) consecutively admitted with DSM-IV diagnosis of AN and fourteen control subjects of similar age were assessed by means of psychopathological scales and functional magnetic resonance imaging (fMRI) during a working memory task. After seven months of treatment and weight recovery, nine AN patients were reassessed. Before treatment, the AN group showed significantly higher activation than controls in temporal and parietal areas and especially in the temporal superior gyrus during performance of the cognitive task. Control subjects did not show greater activation than AN patients in any region. A negative correlation was found between brain activation and body mass index and a positive correlation between activation and depressive symptomatology. At follow-up after weight recovery, AN patients showed a decrease in brain activation in these areas and did not present differences with respect to controls. These results show that adolescent AN patients showed hyperactivation in the parietal and especially the temporal lobe during a working memory task, suggesting that they must make an additional effort to perform at normal levels. This activation correlated with clinical variables. In these young patients, differences with respect to controls disappeared after weight recovery.     

Longitudinal trajectories of hippocampal and prefrontal contributions to episodic retrieval: Effects of age and puberty

The current study investigated longitudinal change in hippocampal and prefrontal contribution to episodic retrieval. Functional neuroimaging data were collected during an item-context association memory task for children between the ages of 8 and 14 with individuals scanned 1–3 times over the course of 0.75–3.7 years (Timepoint 1 N = 90; Timepoint 2 N = 83, Timepoint 3 N = 75). We investigated developmental changes in functional activation associated with episodic retrieval (correct item-context > incorrect item-context contrast) and asked whether pubertal changes contributed to developmental changes in pattern of activation. Non-linear developmental trajectories were observed. In the hippocampus, activation decreased with age during childhood and then increased into early adolescence. In the dorsolateral prefrontal cortex, activation was largely absent initially, but quickly accelerated over time. Independent of age, changes in pubertal status additionally predicted increases in item-context activation in initially older children, and decreases in initially younger children across both regions and two indicators of puberty: the Pubertal Development Scale and salivary testosterone. These findings suggest that changes in both age and pubertal status uniquely contribute to memory-related activation, and the timing of pubertal onset may play an important role in the neural mechanisms supporting memory retrieval.     

Hippocampal complex and retrieval of recent and very remote autobiographical memories: evidence from functional magnetic resonance imaging in neurologically intact people.

It has been argued that the role of the hippocampus in memory is time-limited: during a period of memory consolidation, other brain regions such as the neocortex are said to acquire the ability to support memory retention and retrieval on their own. An alternative view is that retention and retrieval of memory for autobiographical episodes depend on the hippocampal complex, regardless of the age of the memory. We examined the participation of the hippocampal complex in a functional magnetic resonance imaging (fMRI) study in which participants were asked to recollect autobiographical events that occurred either within the last 4 years or more than 20 years ago. We found equivalent levels of hippocampal activation in both conditions in all participants (N = 10). In addition, activation in neocortical regions did not differ as a function of the age of the memory, even though most of the recent memories recalled were less than 2 years old and the remote memories more than 35 years old. The results support the notion that the hippocampal complex participates in retention and recovery of even very old autobiographical memories, and place boundary conditions on theories of memory consolidation.     

Cyclic alternating pattern in infants with congenital hypothyroidism

Congenital hypothyroidism is defined as thyroid hormone deficiency present at birth which is crucial for brain development. Recently, the cyclic alternating pattern, a rhythm present in electroencephalography recordings in non-Rapid eye movement sleep, has been related to brain development and cognition in different pediatric conditions. Therefore, we evaluated the cyclic alternating pattern rate in infants with congenital hypothyroidism, thyroxine supplementation, and healthy controls. The parameters of the cyclic alternating pattern were evaluated in 19 healthy infants (10 female, mean age 25.5?±?15.5?months) and 21 infants diagnosed with congenital hypothyroidism (19 female, mean age 24.3?±?19.0?months). We considered the transient electro-cortical activations (phase A of the cycle) in non-Rapid eye movement sleep and the subdivisions of the A phase in: A1, A2 and A3, based on their frequency content. All subjects were subjected to polysomnography recording in a standard laboratory setting. Sleep data were stored computer following the International 10–20 System. Data showed that congenital hypothyroidism infants exhibited higher frequency of central apnea, hypopnea, and arousals in comparison to controls. Particularly, central apnea index decreased with age in the control group but not in congenital hypothyroidism group. Regarding to cyclic alternating pattern measurements, congenital hypothyroidism infants exhibit a higher frequency in the percentage of A3 subtype (electroencephalographic desynchrony) and conversely a lower percentage of A1 subtype (electroencephalographic synchrony), than healthy infants. An important finding of this study is the positive correlation between A1 mean duration and age, which is bigger in control group than in congenital hypothyroidism group (time duration in control group (0.52?s/month) versus congenital hypothyroidism group (0.1?s/month). Infants with congenital hypothyroidism showed an increase of A3 subtype, of central apnea, and of arousals. The reduction of percentage and mean duration of A1 subtype could be a valuable indicator of sleep development in patients with congenital hypothyroidism and healthy infants.     

Verbal and visuospatial working memory development and deficits in children and adolescents with schizophrenia

Aim: Deficits in working memory are considered a core feature of schizophrenia and are present early in the course of the illness. Because working memory continues to mature through childhood and into early adulthood, it was the aim of this study to assess developmental trajectories of verbal and visuospatial working memory performance in children and adolescents with schizophrenia. Differences in the developmental trajectories in patients compared with controls may reflect differential effects within specific neural networks involved in working memory performance. Methods: Twenty-six children and adolescents with schizophrenia (age range of 8–19 years) and 37 controls matched on age and gender participated in the study. Modified versions of both a verbal and visuospatial Sternberg Item Recognition Paradigm were administered. Results: In the three age groups studied, patients performed significantly worse than controls on the verbal working memory tasks. There were significant effects of diagnosis and load on the verbal Sternberg, with patients performing worse than controls. However, there was no diagnosis by load interactions. Similar findings were present for the visuospatial Sternberg, except for the youngest age group. The 8- to 12-year-old patients had a disproportionately lower performance on the verbal working memory task than on the visuospatial task. Conclusions: Our findings support disruptions in shared verbal and visuospatial working memory networks, such as those supporting encoding processes, in children and adolescents with schizophrenia. We also found specific deficits in non-shared verbal working memory performance in childhood-onset schizophrenia.     

Altered functional adaptation to attention and working memory tasks with increasing complexity in relapsing-remitting multiple sclerosis patients

As attention, processing speed, and working memory seem to be fundamental for a broad range of cognitive performance, the present study on patients with mild forms of relapsing-remitting multiple sclerosis (RR-MS) focused on these domains. To explore subtle neuropsychological changes in either the clinical or fMRI domain, we applied a multistep experimental design with increasing task complexity to investigate global brain activity, functional adaptation, and behavioral responses to typical cognitive processes related to attention and working memory. Fifteen patients with RR-MS (mean age 38 years, 22-49 years, 9 females, mean disease duration 5.9 years (SD = 3.6 years), mean Expanded Disability Status Scale score, 2.3 (SD = 1.3) but without reported cognitive impairment), and 15 age-matched healthy controls (HC; mean age, 34 years, 23-50 years, 6 women) participated. After a comprehensive neuropsychological assessment, participants performed different fMRI experiments testing attention and working memory. In the neuropsychological assessment, patients showed only subtle reduction in learning and memory abilities. In the fMRI experiments, both groups activated the brain areas typically involved in attention and working memory. HC showed a linear in- or decrease in activation paralleling the changing task complexity. Patients showed stronger activation change at the level of the simple tasks and a subsequent saturation effect of (de-)activation at the highest task load. These group/task interaction differences were found in the right parahippocampal cortex and in the middle and medial frontal regions. Our results indicate that, in MS, functional adaptation patterns can be found which precede clinical evidence of apparent cognitive decline.     

Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain

We have examined the influence of thyroid hormone on adult hippocampal neurogenesis, which encompasses the proliferation, survival and differentiation of dentate granule cell progenitors. Using bromodeoxyuridine (BrdU), we demonstrate that adult-onset hypothyroidism significantly decreases hippocampal neurogenesis. This decline is predominantly the consequence of a significant decrease in the survival and neuronal differentiation of BrdU-positive cells. Both the decreased survival and neuronal differentiation of hippocampal progenitors could be rescued by restored euthyroid status. Adult-onset hyperthyroidism did not influence hippocampal neurogenesis, suggesting that the effects of thyroid hormone may be optimally permissive at euthyroid levels. Our in vivo and in vitro results revealed that adult hippocampal progenitors express thyroid receptor isoforms. The in vitro studies demonstrate that adult hippocampal progenitors exhibit enhanced proliferation, survival and glial differentiation in response to thyroid hormone. These results support a role for thyroid hormone in the regulation of adult hippocampal neurogenesis and raise the possibility that altered neurogenesis may contribute to the cognitive and behavioral deficits associated with adult-onset hypothyroidism.     

Differential development of relational memory and pattern separation

Researchers have taken a number of different approaches in their exploration of hippocampal function. One approach seeks to describe hippocampal function by probing the memory representations that the hippocampus supports. Another approach focuses on the role of the hippocampus in pattern separation and completion. Each of these approaches to understanding hippocampal function utilizes a distinct set of specialized tasks, and both of these task sets are known to be sensitive to changes in hippocampal function with age and disease status. But the question remains whether the tasks utilized in these two approaches tap into the same aspects of hippocampal function. We explored this question in the context of hippocampal development. Preadolescent children (N = 73) and young adults (N = 41) completed an identical battery of cognitive tasks consisting of a spatial reconstruction relational memory task, the mnemonic similarity task (MST)—an object‐based pattern separation task, and a novel hybrid task—the Object Discrimination and Distribution (ODD) Task—designed to integrate and simultaneously tax pattern separation and spatial relational memory. Children did not demonstrate impairments in lure discrimination relative to young adults on either the object‐based pattern separation task or for aspects of the ODD task that required pattern separation in the absence of relational memory demands but performed more poorly across aspects of tasks that required relational binding.     

Abnormal hippocampal activation in patients with extensive history of major depression: an fMRI study

Background

Impairment of recollection memory is consistently reported in patients with major depressive disorder (MDD) and may reflect underlying functional hippocampal changes, particularly in those with extensive histories of illness. We hypothesized that relative to controls, patients with a protracted course of illness would show diminished hippocampal activation on functional magnetic resonance imaging (fMRI) during a recollection memory task.

Methods

Patients who experienced 3 or more previously treated depressive episodes were compared with age- and sex-matched controls. We acquired fMRI data while participants performed a recollection memory process dissociation task.

Results

Using bilateral regions of interest (ROIs) prescribed for the right and left hippocampal/ parahippocampal complex, we observed increased activation of the right hippocampal and left parahippocampal gyrus in controls compared with patients with MDD during recollection memory trials. Within-group comparisons revealed heightened engagement of the hippocampal head (R/L) for controls during recollection trials, and greater activation of the hippocampal body/tail (R/L) during the learn-list encoding period in both the MDD and control groups. Recollection memory performance was significantly correlated with changes in blood oxygen level–dependent signal during recollection trials in the ROIs of the right hippocampus and right hippocampal head.

Limitations

This study was limited by the inclusion of patients taking antidepressant medication, raising the possibility that the reported findings were treatment effects.

Conclusion

The findings of decreased recruitment of the right hippocampal and left parahippocampal gyrus in patients with MDD suggest that these regions may be sensitive to the impact of disease burden and repeated episodes of MDD. This attenuated activation may represent stable changes in hippocampal function that occur over the course of illness in patients with MDD. The findings from within-group comparisons show that the group differences in the activation of the right hippocampal head were driven by greater engagement of this region among controls during recollection memory performance. These results also associate recollection performance impairments in patients with MDD with diminished hippocampal engagement.     

High rate of autoimmune thyroiditis in bipolar disorder: lack of association with lithium exposure.

BACKGROUND: We assessed the prevalence of thyroperoxidase antibodies (TPO-Abs) and thyroid failure in outpatients with bipolar disorder compared with two control groups. METHODS: The TPO-Abs of outpatients with DSM-IV bipolar disorder (n = 226), a population control group (n = 252), and psychiatric inpatients of any diagnosis (n = 3190) were measured. Thyroid failure was defined as a raised thyroid stimulating hormone level, previously diagnosed hypothyroidism, or both. Subjects were compared with attention to age, gender, and exposure to lithium. RESULTS: The TPO-Abs were more prevalent in bipolar patients (28%) than population and psychiatric controls (3-18%). The presence of TPO-Abs in bipolar patients was associated with thyroid failure, but not with age, gender, mood state, rapid cycling, or lithium exposure. Thyroid failure was present in 17% of bipolar patients and more prevalent in women. It was associated with lithium exposure, especially in the presence of TPO-Abs, but not with current rapid cycling, although an association may have been masked by thyroid hormone replacement. CONCLUSIONS: Thyroid autoimmunity was highly prevalent in this sample of outpatients with bipolar disorder and not associated with lithium treatment. These variables appear to be independent risk factors for the development of hypothyroidism, especially in women with bipolar disorder.     

Hypothyroidism following developmental iodine deficiency reduces hippocampal neurogranin,CaMK II and calmodulin and elevates calcineurin in lactational rats

Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal neurogranin, calcium/calmodulin dependent protein kinase II (CaMKII), calmodulin (CaM) and calcineurin (CaN) are implicated in the brain impairment in lactational rat hippocampus following developmental ID and hypothyroidism. Three developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 21. Then, the neurogranin, CaMKII, CaM and CaN in the hippocampus were detected with immunohistochemistry and western blotting on PN14 and PN21. The iodine-deficient and hypothyroid pups showed significantly lower level of neurogranin, CaMKII and CaM and significantly increased CaN in hippocampal CA1 and CA3 regions than the controls on PN14 and PN21 (P < 0.05, respectively). Data indicate that, in lactational rats, hippocampal neurogranin, CaMKII, CaM and CaN are involved in the brain impairment by developmental ID and hypothyroidism.