Early Post-Natal Iron Administration Induces Astroglial Response in the Brain of Adult and Aged Rats

This study was aimed to investigate neuropathological changes in adult and aged rats subjected to supplementary iron administration in a critical postnatal period to study the contribution of environmental risk factors to the pathogenesis of neurodegenerative disorders. Ten rats received a single daily oral administration of iron (10 mg/kg) between 12th and 14th post-natal days; nine rats received vehicle (sorbitol 5% in water) in the same period. Five iron-treated and three sorbitol-treated rats were killed at the age of 3 months while five iron-treated and six sorbitol-treated rats were killed at age of 24 months and their brains processed for immunohistochemistry. Increased astrocytosis, revealed by densitometry of GFAP-immunoreactive astrocytes, was found in aged (24 months) iron-treated rats in the substantia nigra and striatum and in the hippocampus of adult (3 months) iron-treated rats when compared to age-matching controls. Decreased densitometry of neurons, revealed by neuronal nucleus immunohistochemistry, was found in aged (24 months) iron-treated rats in substantia nigra and striatum when compared to age-matching controls. These findings suggest that transient dietary iron supplementation during the neonatal period is associated to cellular imprinting in the brain later in life.     

针刺预处理对短暂性脑缺血再灌注损伤海马神经元的保护

The present study established a model of brain ischemia in aged rats using four-vessel occlusion.We observed hippocampal CA1 neuronal apoptosis and apoptosis-mediated protease caspase-3 expression following preconditioning of electroacupuncture at Baihui(GV 20).Our results showed that the number of hippocampal CA1 normal neurons was decreased,and degenerated neurons were increased 12 hours to 3 days following cerebral ischemia/reperfusion.The number of hippocampal CA1 apoptotic neurons and caspase-3-positive neurons in rats with cerebral ischemia/reperfusion injury was significantly decreased following acupuncture preconditioning.Acupuncture preconditioning protects aged rats against ischemia/reperfusion injury by regulating caspase-3 protein expression.     

Aging is neuroprotective during global ischemia but leads to increased caspase-3 and apoptotic activity in hippocampal neurons

Previously, we found a significantly greater number of surviving CA1 neurons to global ischemia in the aged (24-month-old) F344 rats than in young (4-month-old) rats. The present study tests the hypothesis that aging retards neuronal death in the hippocampal CA1 region following cerebral ischemia. The CA1 "living cell ratio" was significantly greater in aged than in young rats at three days (62+/-8% vs. 30+/-8%) and at eight days (36+/-6% vs. 17+/-5%), but not at 14 days (15+/-12% vs. 18+/-12%) following ischemia. The number of the CA1 cells exhibiting co-localized TdT-mediated X-dUTP nick end labeling reaction and caspase-3 active peptide (C3AP) immunoreactivity was greater in aged than young animals at three and eight days following ischemia (36+/-8/mm vs. 3+/-1/mm and 36+/-14 vs. 0+/-0, p<0.05 respectively). Also, the total number of C3AP-positive cells in the CA1 region in the aged group was significantly greater than in the young group at three and eight days post-ischemia (p<0.05). Aging appears to delay caspase-3-dependent apoptotic cell death induced by global ischemia in the CA1 region of the hippocampus, consistent with an age-induced neuroprotective process.     

Aging impairs the late phase of long-term potentiation at the medial perforant path-CA3 synapse in awake rats

The effects of aging on long-term potentiation (LTP) in the dentate gyrus (DG) and CA1 are well documented, but LTP at the medial perforant path (MPP)-CA3 synapse of aged animals has remained unexplored. Because the MPP-DG and Schaffer-collateral-CA1 synapses account for only about 20% of total hippocampal synapses, global understanding of how aging affects hippocampal plasticity has remained limited. Much is known about LTP induction in the hippocampal formation, whereas the mechanisms that regulate LTP maintenance are less understood, especially during aging. We investigated the effects of aging on MPP-CA3 LTP induction and maintenance in awake rats. As is the case in the DG and CA1, high-frequency stimulation-induced LTP at the MPP-CA3 synapse is normal in aged rats. These data indicate that N-methyl-D-aspartate (NMDA) receptor-mediated processes are intact at the MPP-CA3 synapse in aged rats. In contrast, aging impaired the magnitude and duration of MPP-CA3 LTP over a period of days. Also, these data are consistent with reports that area CA3 is especially susceptible to age-related changes. Our data suggest that aging impairs mechanisms that regulate the late phase of MPP-CA3 LTP and contribute to a more global understanding of how aging affects hippocampal plasticity.     

Differential activation of c-fos and caspase-3 in hippocampal neuron subpopulations following neonatal hypoxia-ischemia

Neonatal hypoxia-ischemia (HI) induces immediate early gene (IEG) c-fos expression as well as neuron death. The precise role of IEGs in neonatal HI is unclear. We investigated the temporal and spatial patterns of c-Fos expression in postnatal day 7 mice after unilateral carotid ligation and exposure to 8% oxygen. mRNA levels of c-fos quantitated by real-time polymerase chain reaction (PCR) increased nearly 40-fold (log 1.2 +/- 0.4) in the ipsilateral hippocampus 3 hr following neonatal HI, then returned to basal levels within 12 hr, although no change was observed in c-jun mRNA. Frozen coronal brain sections were stained with cresyl violet or used for immunohistochemical detection of c-Fos, cleaved caspase-3, glial fibrillary acidic protein (GFAP), and the mature neuron marker NeuN. c-Fos immunoreactivity increased throughout the injured hippocampus 3 hr after HI but became restricted to the CA2-3 subregion and the dentate gyrus (DG) at 6-12 hr and declined by 24 hr. In contrast, cleaved (activated) caspase-3 immunoreactivity was most abundant in the ipsilateral CA1 region at 3-6 hr after neonatal HI, then became more prominent in CA2-3 and DG. Double-labeling experiments showed c-Fos and cleaved caspase-3 immunoreactivity localized in spatially distinct neuron subpopulations. Prominent c-Fos immunoreactivity was observed in surviving CA2-3 and external granular DG neurons, and robust cleaved caspase-3 immunoreactivity was observed in pyknotic CA1, CA2-3, and subgranular DG neurons. The differential expression of c-Fos in HI-resistant hippocampal subpopulations vs. cleaved caspase-3 in dying neurons suggests a neuroprotective role for c-Fos expression in neonatal HI.     

Brief novelty exposure facilitates dentate gyrus LTP in aged rats

Aging is associated with a decreased capacity for dentate gyrus (DG) granule cell depolarization as well as reduced perforant path activation. Although it is well established that the maintenance of DG long-term potentiation (LTP) over days is impaired in aged, as compared to young animals, the threshold for inducing this LTP has never been investigated in aged, awake animals. In addition, although exposure to novelty prior to theta-burst stimulation (TBS) increases both the induction and longevity of DG LTP in adult rats, the effects of exposure to novelty on LTP in aged rats have never been investigated. Here, we report that although TBS delivered in the home cage induces robust and long-lasting DG LTP in young rats, TBS fails to induce DG LTP in aged rats. Interestingly, delivery of TBS to aged rats exploring novel environments induces robust and long-lasting LTP, with the induction, but not the longevity, of this LTP being similar in magnitude to that observed in young rats delivered TBS in the home cage. These results indicate that although TBS-induced DG LTP is impaired in aged, as compared to young rats, TBS during exploration of novel environments is sufficient to rescue age-related deficits in DG LTP. We discuss these observations in the context of previous findings suggesting that the facilitation of LTP by exposure to novel environments results as a consequence of reduced network inhibition in the DG and we suggest that, in spite of age-related changes in the DG, this capacity persists in aged rats and represents a nondietary and nonpharmacological way to facilitate DG LTP during aging.     

Heterogeneity of Age-Related Neural Hyperactivity along the CA3 Transverse Axis

Age-related memory deficits are correlated with neural hyperactivity in the CA3 region of the hippocampus. Abnormal CA3 hyperactivity in aged rats has been proposed to contribute to an imbalance between pattern separation and pattern completion, resulting in overly rigid representations. Recent evidence of functional heterogeneity along the CA3 transverse axis suggests that proximal CA3 supports pattern separation while distal CA3 supports pattern completion. It is not known whether age-related CA3 hyperactivity is uniformly represented along the CA3 transverse axis. We examined the firing rates of CA3 neurons from young and aged, male, Long–Evans rats along the CA3 transverse axis. Consistent with prior studies, young CA3 cells showed an increasing gradient in mean firing rate from proximal to distal CA3. However, aged CA3 cells showed an opposite, decreasing trend, in that CA3 cells in aged rats were hyperactive in proximal CA3, but possibly hypoactive in distal CA3, compared with young (Y) rats. We suggest that, in combination with altered inputs from the entorhinal cortex and dentate gyrus (DG), the proximal CA3 region of aged rats may switch from its normal function that reflects the pattern separation output of the DG and instead performs a computation that reflects an abnormal bias toward pattern completion. In parallel, distal CA3 of aged rats may create weaker attractor basins that promote abnormal, bistable representations under certain conditions.SIGNIFICANCE STATEMENT Prior work suggested that age-related CA3 hyperactivity enhances pattern completion, resulting in rigid representations. Implicit in prior studies is the notion that hyperactivity is present throughout a functionally homogeneous CA3 network. However, more recent work has demonstrated functional heterogeneity along the CA3 transverse axis, in that proximal CA3 is involved in pattern separation and distal CA3 is involved in pattern completion. Here, we show that age-related hyperactivity is present only in proximal CA3, with potential hypoactivity in distal CA3. This result provides new insight in the role of CA3 in age-related memory impairments, suggesting that the rigid representations in aging result primarily from dysfunction of computational circuits involving the dentate gyrus (DG) and proximal CA3.     

Interleukin‐1β‐immunoreactive neurons in the hippocampus and paraventricular nucleus of the hypothalamus after stress stimulation in aged versus adult rats

It is believed that the impact of stress on interleukin‐1β (IL‐1β) depends on the ontogenetic age. This study examines the influence of acute or chronic exposure to forced‐swim (FS) stress or high‐light open‐field (HL‐OF) stimulation on the expression of IL‐1β. Double immunofluorescence staining was used to reveal the density of IL‐1β/NeuN (NeuN is a neuronal nuclear marker)‐immunoreactive (‐ir) cells in the hippocampal subfields CA1 and CA3, dentate gyrus (DG), and paraventricular nucleus (PVN) of the hypothalamus. Adult postnatal day 90 (P90) and aged (P720) rats were used in this experiment. The data showed a significant increase in the density of IL‐1β/NeuN‐ir cells in the CA1, CA3, DG, and PVN in P720 nonstressed rats in relation to P90 control animals. Neither FS nor HL‐OF acute stimulation caused alteration in the density of IL‐1β‐ir neurons in any of the investigated structures in P90 and P720 rats in comparison with control groups. However, chronic FS caused a significant increase in CA3 and DG of P720 rats, and chronic HL‐OF led to a significant increase in the density of IL‐1β‐ir neurons in the PVN of P90 rats and in all hippocampal subfields of P720 animals. These results indicate that chronic HL‐OF stimulation is a factor that induces changes in the number of IL‐1β‐ir neurons in the PVN of adult rats, whereas both chronic FS and HL‐OF are aggravating factors for the hippocampus of aged (P720) animals. © 2014 Wiley Periodicals, Inc.     

Erythropoietin preconditioning on hippocampus neuronal apoptosis following status epilepticus induced by Li-pilocarpine in rats through anti-caspase-3 expression

Selective neuronal loss following status epilepticus (SE) was first described just under 100 years ago. The acute pathology following SE was shown to be 'ischemic cell change' and was assumed to arise through hypoxia/ischemia. Recently, erythropoietin (Epo) has been shown to have potent anti-apoptosis activity in central nervous system neurons in animal models of ischaemic injury. AIMS: In this report, in order to determine Epo preconditioning on hippocampus neuronal apoptosis, we examined caspase-3 expression following SE caused by Li-pilocarpine in rats. SETTINGS AND DESIGN: Animals were classified into three groups: EP group (pilocarpine group), rhEpo-pilocarpine group and control group. Four hours after preconditioning with Epo intraperitoneally, pilocarpine hydrochloride was administered intraperitoneally and observed for behavioral manifestations of SE. The animals were sacrificed at one hour after SE onset. MATERIALS AND METHODS: At the above-mentioned time point, animals were deeply anesthetized and were perfused through the left ventricle. Detection of hippocampus neuronal apoptosis was performed with caspase-3 immunohistochemical technique on three groups. To further confirm which cell population upregulates caspase-3, brain sections were stained for NeuN (green) and caspase-3 (red). STATISTICAL ANALYSIS: ANOVA and Fisher's post hoc test was used. RESULTS: Quatification of hippocampus neurons revealed that the number of caspase-3-positive cells in the CA1/CA3 area and dentate gyrus(DG) of three groups had a significant difference. In comparison with control group, there was an increase by 74% and 534%, 42% and 272% in the CA1/CA3 area and DG of EP group and rhEpo-treated group respectively. There was a decrease by 18% and 26% in the CA1/CA3 area and DG of rhEpo-treated group compared with those in EP group. In addition, colocalization of caspase-3 with NeuN was shown. CONCLUSIONS: Systemic rhEpo therapy reduced caspase-3 expression in SE induced by Li-pilocarpine.     

Influence of age or circadian time on Bcl-2 and Bax mRNA expression in the rat hippocampus after corticosterone exposure

A rapid elevation in the level of endogenous corticosterone (CORT) functions in the stress response associated with the hypothalamus-pituitary-adrenal axis, and it has been well documented that high levels of CORT play neurotoxic roles in the hippocampus. Both aging and the circadian rhythm possibly affect the sensitivity to CORT, although their endogenous modifications in the CORT-mediated events remain unclear. To explore the influence of age or circadian time on hippocampal vulnerability to excess CORT, we examined the relative mRNA expression of bcl-2 and bax in the dentate gyrus (DG) and the CA1 subfield, compared with the CA3 as an internal standard, after acute CORT administration using in situ RT-PCR. Male rats aged 10 weeks (young) or 6 months (adult) were treated with CORT at 0800 or 2000 h. The bcl-2 to bax mRNA ratio in the dentate gyrus (DG) was significantly decreased 2h after CORT exposure in the young rats treated at 0800 or 2000 h. In the adult rats, the treatment with CORT at 0800 h significantly decreased the bcl-2 to bax ratio, whereas the treatment at 2000 h was ineffective; the discrepancy between the treatment time points was apparent in adult rats, but not in young rats. Our results emphasize the importance of circadian time as well as age as a factor influencing the stress paradigm.     

Role of phosphorylated CaMKII and calcineurin in the differential effect of hypothyroidism on LTP of CA1 and dentate gyrus

Hypothyroidism impairs early long-term potentiation (LTP) in the CA1 but not in the dentate gyrus (DG) of hippocampus of anesthetized adult rats. Protein levels and activities of signaling molecules in both the CA1 and DG of surgically thyroidectomized and sham-operated euthyroid rats were measured. Basal levels of total calmodulin kinase II (CaMKII) protein in both the CA1 and DG were decreased in hypothyroidism. Marked reduction of basal P-CaMKII levels and CaMKII activity was seen in CA1, but not in the DG of the same hypothyroid animals. Basal levels of calmodulin and protein kinase Cgamma (PKCgamma) were decreased in CA1 but remained unchanged in the DG of hypothyroid rats. Basal calcineurin levels and activity, although enhanced in CA1, were reduced in the DG of hypothyroid rats. These findings suggest that the DG may possess a compensatory mechanism whereby calcineurin levels are reduced, to allow sufficient CaMKII activity to produce an apparently normal LTP in hypothyroid rats.     

Age‐related changes of cornu ammonis 1 pyramidal neurons in gerbil transient ischemia

This study reports that postischemic apoptotic cell death of the hippocampal cornu ammonis (CA) 1 neurons is delayed in aged gerbils. Age‐related changes in the process of CA1 neuronal death following transient ischemia was studied. Two groups of Mongolian gerbils were used in this study, which compared adult (4‐month‐old) and aged (24‐month‐old) animals by hematoxylin–eosin stain, in situ nick‐end labeling (TUNEL method) and electron microscopy. In the process of neuronal death, neuronal loss of the aged group was histologically less severe than that of the adult group. TUNEL‐positive cells were found on days 3–5 after ischemia in the adult group, while they were still found on day 7 in the aged group. The apoptotic process of the aged group was delayed compared to the adult group. Furthermore, lipofuscin was ultrastructurally observed inside the apoptotic body 5 days after ischemia in CA1 pyramidal neurons of the aged group. It is likely that colocalization of lysosomal enzyme cathepsin D with lipofuscin might be associated with the age‐related alteration of lysosomal system in the neurons. Altogether these data suggest that age‐related lysosomal changes might affect the apoptotic cascade process in postischernic CA1 neurons.     

Total antioxidant capacity is impaired in different structures from aged rat brain

Our data support a disproportion between free radicals levels and scavenging systems activity in different cerebral regions of the aging rat. We investigated the total reactive antioxidant potential and reactivity levels, which represent the total antioxidant capacity, in different cerebral regions of the aging rat (cortex, striatum, hippocampus and the cerebellum). In addition, we have determined several oxidative stress parameters, specifically the free radicals levels, the macromolecules damage (lipid peroxidation and carbonyl content), as well as the antioxidant enzymes activities in different cerebral areas from young (2 months-old), mature adult (6 months-old) and old (24 months-old) male Wistar rats. Free radicals levels, determined by 2′,7′-dichlorofluorescein diacetate probe, were higher in striatum, cerebellum and hippocampus from aged rats. There was an age-related increase in lipoperoxidation in hippocampus and cerebral cortex. In the cerebellum, a high activity of superoxide dismutase and a decrease of catalase activity were observed. The striatum exhibited a significant catalase activity decrease; and glutathione peroxidase activity was diminished in the hippocampus of mature and aged rats. There was a marked decrease of total antioxidant capacity in hippocampus in both reactivity and potential levels, whereas striatum and cerebral cortex displayed a reduction on reactivity assay. We suggest that age-related variations of total antioxidant defenses in brain may predispose structures to oxidative stress-related neurodegenerative disorders.     

Vulnerability of the Dentate Gyrus to Aging and Intracerebroventricular Administration of Kainic Acid

The hippocampal formation is highly vulnerable to the aging process, demonstrating functional alterations in circuitry with aging. Aging may also change the sensitivity of the hippocampal formation to excitotoxic lesions. In this study, using young adult, middle aged, and aged Fischer 344 rats, we evaluated morphometric changes in the dentate gyrus as a function of age and also in response to an administration of an excitotoxin (kainic acid) into the right lateral ventricle. The dentate gyrus was measured for changes in the area of dentate hilus and the dentate granule cell layer, alterations in the width of the dentate granule cell layer, and degree of dentate hilar cell loss. With aging, the hilar area increased in size while the area and width of the dentate granule cell layer remained constant. However, the most striking change with aging was a significant reduction in the number of dentate hilar neurons. Intracerebroventricular kainic acid produced consistent lesions in the entire ipsilateral CA3 region, and the size of CA3 lesion was identical in all three ages of animals. Following the lesion, areas of both the dentate hilus and the granule cell layer were significantly decreased in only young adult and middle aged animals whereas the width of the dentate granule cell layer was significantly increased only in the middle aged group. In contrast, dentate hilar neurons were significantly reduced in all ages of animals with the maximum reductions in neuron number observed in the aged group. Thus, aging in the dentate gyrus is characterized by a significantly decreased number of dentate hilar neurons and also a significantly increased susceptibility of dentate hilar neurons to excitotoxic damage.     

Participation of par-4 in the degeneration of striatal neurons induced by metabolic compromise with 3-nitropropionic acid

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by chorea, psychiatric disturbances, and dementia. It is caused by a polyglutamine repeat expansion in the huntingtin protein. The striatum is a major site of neuronal loss in HD, but the mechanisms underlying the neurodegenerative process have not been established. Systemic administration of the succinate dehydrogenase inhibitor 3-nitropropionic acid (3NP) to rodents results in motor dysfunction and degeneration of striatal neurons with features similar to those of HD. Here we report that levels of prostate apoptosis response-4 (Par-4; a protein recently linked to neuronal apoptosis) increase in striatum, and to a lesser extent in cortex and hippocampus, after systemic administration of 3NP to adult rats. The increase in Par-4 levels occurred within 6 h of 3NP administration and was followed by an increase in caspase activation which preceded neuronal loss. Exposure of cultured primary striatal neurons to 3NP induced a rapid increase of Par-4 levels and caspase activation. Treatment of striatal neurons with a Par-4 antisense oligonucleotide blocked Par-4 induction by 3NP, suppressed caspase activation, and attenuated neuronal apoptosis. The caspase-3 inhibitor DEVD suppressed 3NP-induced apoptosis of striatal neurons, but did not prevent induction of Par-4, indicating that Par-4 acts upstream of caspase-3 activation in the cell death pathway. Our results suggest that Par-4 plays an important role in the degeneration of striatal neurons in an experimental model of HD.     

Neuronotrophic activity for ciliary ganglion neurons. Induction following injury to the brain of neonatal, adult, and aged rats

The induction of neuronotrophic activity following injury to the brain of neonatal, adult, and aged Sprague-Dawley rats was compared using an improved in vitro assay. The maximal levels of activity in tissue surrounding the wound were reached at 3, 10-15, and about 15 days postlesion in neonatal, adult, and aged animals, respectively. Tissue neuronotrophic levels were always much lower in neonatal animals relative to the older animals. Accumulation of neuronotrophic activity in the gelfoam placed into the wound cavities in neonatal and adult animals lagged behind the levels in tissue by 4-5 days, suggesting that either the neuronotrophic factor itself or the cells which produce it are transferred from the tissue into the gelfoam. Relatively little activity accumulated in the gelfoam taken from aged Sprague-Dawley rats, and this observation was confirmed in aged Fischer rats. Aged animals seem to be unable to produce or release one of a number of neuronotrophic factors in response to injury.     

Aging blunts ischemic-preconditioning-induced neuroprotection following transient global ischemia in rats

The present study examines the hypothesis that aging defined by the 50% survival age compromises neuroprotection afforded by ischemic preconditioning (IPC). Sixty-four male F344 rats aged 4- and 24-months, respectively, were subjected to IPC, (3-min ischemia) or sham-surgery followed by 10-min (full) ischemia or sham-surgery 2 days later. There were 4 groups at each age: sham-surgery-sham-surgery (SS), preconditioning-sham-surgery (PS), preconditioning-ischemia (PI) and sham-surgery-ischemia (SI) groups. Assessments of histology and immunoreactivities of N-methyl-D-aspartic acid receptor 1 (NMDAr1) and caspase-3 active peptide (C3AP) in the hippocampal CA1 region were performed 8 days after full ischemia. The CA1 "living cell ratio" was greater in the aged SI group than in the young SI group (32+/-6% vs. 17+/-5%, p<0.05), whereas the degree of protection against full ischemia afforded by IPC was reduced in the aged compared with the young (53+/-17% vs. 241+/-25%, P<0.0001). The basal level of NMDAr1 immunofluorescence was significantly higher in young animals, while the numbers of C3AP-positive cells were greater in all three aged ischemic groups as compared to respective young groups (p<0.01, p=0.055 and p<0.05). A fourth method of assessing cell damage using Fluoro Jade C labeled degenerating neurons that were also intensively eosinophilic. Counts of Fluoro Jade C-positive cells were higher in the young SI group than in the aged SI group (P<0.05), suggesting that mechanisms of ischemic cell death may change with aging. In conclusion, aging alters mechanisms of ischemic cell death in CA1 neurons and ischemic tolerance mechanisms are blunted by aging.     

Differential induction of nerve growth factor and basic fibroblast growth factor mRNA in neonatal and aged rat brain

Stimulation of glucocorticoid or β-adrenergic receptors (BAR) has been shown to increase nerve growth factor (NGF) biosynthesis in adult rat brain. Little is known about the role of these receptors in the regulation of NGF expression in neonatal and aged brain. We have examined the effect of the synthetic glucocorticoid dexamethasone (DEX) and the BAR agonist clenbuterol (CLE) on the levels of NGF mRNA in neonatal (8 day old), adult (3 month old) and aged (24 month old) rats. By 3 h, DEX (0.5 mg/kg, s.c.) evoked a comparable increase in NGF mRNA in the cerebral cortex and hippocampus in both 8-day and 3-month-old rats. In contrast, CLE (10 mg/kg, i.p.) failed to change NGF mRNA levels in neonatal rats, while increasing (2–3-fold) NGF mRNA levels in the cerebral cortex of adult rats. In 24-month-old rats, both DEX and CLE elicited only a modest increase in NGF mRNA. This increase was, however, anatomically and temporally similar to that observed in adult animals. The weak effect of DEX or CLE was not related to a down-regulation of receptor function because both DEX and CLE were able to elicit a comparable increase in the mRNA levels for basic fibroblast growth factor (FGF2) in neonatal, adult and aged rat brain. Our data demonstrate that induction of NGF expression by neurotransmitter/hormone receptor activation varies throughout life and suggest that pharmacological agents might be useful tools to enhance trophic support in aging.     

Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

Pregnancy is a complex process, involving a number of hormones and trophic factors, many of which are formed in the placenta. Several of these trophic factors have an effect at the neuronal level, such as BDNF. Consequently, recent reports have shown that exposure to these hormones (estrogen and progesterone) and trophic factors such as BDNF exert a neuroprotective effect. Here, we study the effect of the number of pregnancies on dendritic morphology of aged female rats (18 months of age). Rats of the 18‐month‐old Sprague Dawley strain with zero, one, two, and three gestations were evaluated for locomotor activity, and Golgi–Cox stain was performed to evaluate the dendritic morphology parameters, the number of dendritic spines, total dendritic length, and branching order number. Adult nulliparous rats (3 months of age) were used as another control group. Adult nulliparous and aging rats with two pregnancies showed an increase in locomotor activity. Adult nulliparous showed an increase in the dendritic spine number compared to old nulliparous rats in both layers of the PFC, the DG, and NAcc. Old rats with two and three pregnancies also showed an increase in the number of dendritic spines compared to old nulliparous rats in layers 3 and 5 of the PFC and in the CA1. Aging animals with one pregnancy also showed an increase in dendritic length compared to old nulliparous rats in the CA1. Our results clearly suggest that two and three pregnancies increase the dendritic spines number in the PFC and CA1 of aged female rats.