Early neonatal inflammation affects adult pain reactivity and anxiety related traits in mice: genetic background counts

Protracted or recurrent pain and inflammation in the early neonatal period may cause long-lasting changes in central neural function. However, more research is necessary to better characterize the long-term behavioral sequelae of such exposure in the neonatal period. Objectives: (1) to study whether timing of postnatal exposure to persistent inflammation alters responsiveness to thermal pain in the adult animal; (2) to assess whether animals experiencing early postnatal chronic inflammation display altered anxiety related behavior; (3) to study the importance of genetic background. Newborn mice (outbred strain, CD1 and F1 hybrid strain, B6C3F1) received an injection of Complete Freund's Adjuvant (CFA) or saline on either postnatal day 1 or 14 (PND1; PND14) into the left hind paw. Pain to radiant heat and anxiety were examined in 12-week-old adult animals. Adult baseline PWL was significantly decreased in CD1 mice exposed to CFA on PND 1 and 14 as compared to their saline treated counterparts. B6C3F1 mice exposed to CFA on PND14 showed markedly reduced baseline PWL compared to the PND14 saline group. Persistent inflammation experienced by B6C3F1 mice on PND1 failed to affect baseline adult thermal responsiveness. Adult mice, CD1 and B6C3F1, displayed low anxiety traits only if they had been exposed to persistent inflammation on PND1 and not on PND14. Our research suggests a role for genetic background in modulating long-term behavioral consequences of neonatal persistent inflammation: the data support the hypothesis that pain experienced very early in life differentially affects adult behavioral and emotional responsiveness in outbred (CD1) and hybrid mice (B6C3F1).     

Corpus callosum infarction: radiological and histological findings

Journal of Neurology -     

Open-source open-access reaction time test (OORTT): an easy tool to assess reaction times

Neurological Sciences - The speed of information processing is one of the most reliable indices of cognitive efficiency. The most common way to evaluate this ability is to assess reaction times...     

Environmental enrichment potentiates thalamocortical transmission and plasticity in the adult rat visual cortex

It has been demonstrated that the complex sensorimotor and social stimulation achieved by rearing animals in an enriched environment (EE) can reinstate juvenile‐like plasticity in the adult cortex. However, it is not known whether EE can affect thalamocortical transmission. Here, we recorded in vivo field potentials from the visual cortex evoked by electrical stimulation of the dorsal lateral geniculate nucleus (dLGN) in anesthetized rats. We found that a period of EE during adulthood shifted the input–output curves and increased paired‐pulse depression, suggesting an enhanced synaptic strength at thalamocortical terminals. Accordingly, EE animals showed an increased expression of the vesicular glutamate transporter 2 (vGluT‐2) in geniculocortical afferents to layer IV. Rats reared in EE also showed an enhancement of thalamocortical long‐term potentiation (LTP) triggered by theta‐burst stimulation (TBS) of the dLGN. To monitor the functional consequences of increased LTP in EE rats, we recorded visual evoked potentials (VEPs) before and after application of TBS to the geniculocortical pathway. We found that responses to visual stimulation were enhanced across a range of contrasts in EE animals. This was accompanied by an up‐regulation of the intracortical excitatory synaptic marker vGluT‐1 and a decrease in the expression of the vesicular GABA transporter (vGAT), indicating a shift in the excitation/inhibition ratio. Thus, in the adult rat, EE enhances synaptic strength and plasticity of the thalamocortical pathway associated with specific changes in glutamatergic and GABAergic neurotransmission. These data provide novel insights into the mechanisms by which EE shapes the adult brain. © 2010 Wiley‐Liss, Inc.     

Characteristics of phonological development as a risk factor for language development in Italian-speaking pre-term children: A longitudinal study

This study analysed the early linguistic development of Italian pre-term children. Samples of spontaneous pre-linguistic and verbal production were recorded at 12 and 18 months of age from two groups of children: 24 pre-term children and 15 full-term children. The Italian version of the MacArthur-Bates Questionnaire was administered at 24 months of age. Comparisons between these two groups reveal differences in many aspects of phonetic and phonological development, such as consonantal inventory at 12 and 18 months of age and syllabic babbling complexity at 18 months of age. Results evidenced that birth weight was related with phonological skills exhibited at 18 months of age, and these skills in turn are related with vocabulary size at 24 months of age. Data are discussed within a theoretical framework that hypothesizes that early phonetic abilities have long-lasting effects on the process of language acquisition.     

Neuroprotective and anti‐inflammatory effects of the adenosine A2A receptor antagonist ST1535 in a MPTP mouse model of Parkinson's disease

Adenosine A_2A receptor antagonists are one of the most attractive classes of drug for the treatment of Parkinson's disease (PD) as they are effective in counteracting motor dysfunctions and display neuroprotective and anti‐inflammatory effects in animal models of PD. In this study, we evaluated the neuroprotective and anti‐inflammatory properties of the adenosine A_2A receptor antagonist ST1535 in a subchronic 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of PD. C57BL/6J mice were repeatedly administered with vehicle, MPTP (20 mg/kg), or MPTP + ST1535 (2 mg/kg). Mice were sacrificed three days after the last administration of MPTP. Immunohistochemistry for tyrosine hydroxylase (TH) and cresyl violet staining were employed to evaluate dopaminergic neuron degeneration in the substantia nigra pars compacta (SNc) and caudate‐putamen (CPu). CD11b and glial fibrillary acidic protein (GFAP) immunoreactivity were, respectively, evaluated as markers of microglial and astroglial response in the SNc and CPu. Stereological analysis for TH revealed a 32% loss of dopaminergic neurons in the SNc after repeated MPTP administration, which was completely prevented by ST1535 coadministration. Similarly, CPu decrease in TH (25%) was prevented by ST1535. MPTP treatment induced an intense gliosis in both the SNc and CPu. ST1535 totally prevented CD11b immunoreactivity in both analyzed areas, but only partially blocked GFAP increase in the SNc and CPu. A_2A receptor antagonism is a new opportunity for improving symptomatic PD treatment. With its neuroprotective effect on dopaminergic neuron toxicity induced by MPTP and its antagonism on glial activation, ST1535 represents a new prospect for a disease‐modifying drug. Synapse, 2010. © 2010 Wiley‐Liss, Inc.     

Reduced language lateralization in first-episode medication-naive schizophrenia

Diminished functional lateralization in language-related areas is found in chronic schizophrenia. It is not clear at what stage of illness these abnormalities in lateralization arise, or whether they are affected by medication. In addition, it is hypothesized that reduced language lateralization is related to positive symptoms of schizophrenia, but studies addressing this issue have yielded contradictory results. In this study we used functional MRI to measure language lateralization in 35 first-episode medication-naive schizophrenia patients and 43 matched healthy controls. Subjects performed three language tasks: a paced verb generation task, an antonym generation task, and a semantic decision task. Lateralization Index (LI) was calculated, using a relative threshold technique, in seven Regions of Interest (ROIs), including the main language-related areas and their contralateral homologues. In addition, we investigated whether language lateralization was correlated with psychotic symptoms. Across all ROIs, LI was significantly reduced in patients (p<0.001) compared to controls. Post-hoc tests revealed that this reduction was most prominent in the inferior frontal gyrus (part of Broca's area) (p=0.003) and the superior temporal gyrus (part of Wernicke's area) (p<0.001). LI was not correlated with the positive subscale of the PANSS, nor with hallucinations or disorganization. This is the first study to report reduced LI at the onset of schizophrenia, before medical treatment is initiated.     

Central effects of a local inflammation in three commonly used mouse strains with a different anxious phenotype

As in humans, genetic background in rodents may influence a peculiar set of behavioural traits such as sensitivity to pain and stressors or anxiety-related behaviours. Therefore, we tested the hypothesis that mice with different genetic backgrounds [outbred (CD1), inbred (C57BL/6J) and hybrid (B6C3F1) adult male mice] display altered reactivity to pain, stress and anxiety related behaviours.We demonstrated that B6C3F1 mice displayed the more anxious phenotype with respect to C57BL/6J or CD1 animals, with the latter being the less anxious strain when tested in an open field and on an elevated plus maze. No difference was observed across strains in thermal sensitivity to a radiant heat source. Mice were then treated with a sub-plantar injection of the inflammatory agent Complete Freund's Adjuvant (CFA), 24 h later they were hyperalgesic with respect to saline exposed animals, irrespective of strain. We then measured intra-strain differences and CFA-induced inter-strain effects on the expression of various genes with a recognized role in pain and anxiety: BDNF, IL-6, IL-1β, IL-18 and NMDA receptor subunits in the mouse thalamus, hippocampus and hypothalamus. The more anxious phenotype observed in B6C3F1 hybrid mice displayed lower levels of BDNF mRNA in the hippocampus and hypothalamus when compared to outbred CD1 and C57BL/6J inbred mice. CFA led to a general decrease in central gene expression of the evaluated targets especially in CD1 mice, while BDNF hypothalamic downregulation stands out as a common effect of CFA in all three strains evaluated.