Changes In Adult Brain Research Articles

Risperidone administered during adolescence induced metabolic, anatomical and inflammatory/oxidative changes in adult brain: A PET and MRI study in the maternal immune stimulation animal model

Inflammation and oxidative stress (IOS) are considered key pathophysiological elements in the development of mental disorders. Recent studies demonstrated that the antipsychotic risperidone elicits an antiinflammatory effect in the brain. We administered risperidone for 2-weeks at adolescence to assess its role in preventing brain-related IOS changes in the maternal immune stimulation (MIS) model at adulthood. We also investigated the development of volumetric and neurotrophic abnormalities in areas related to the HPA-axis. Poly I:C (MIS) or saline (Sal) were injected into pregnant Wistar rats on GD15. Male offspring received risperidone or vehicle daily from PND35-PND49. We studied 4 groups (8–15 animals/group): Sal-vehicle, MIS-vehicle, Sal-risperidone and MIS-risperidone. [18F]FDG-PET and MRI studies were performed at adulthood and analyzed using SPM12 software. IOS and neurotrophic markers were measured using WB and ELISA assays in brain tissue. Risperidone elicited a protective function of schizophrenia-related IOS deficits. In particular, risperidone elicited the following effects: reduced volume in the ventricles and the pituitary gland; reduced glucose metabolism in the cerebellum, periaqueductal gray matter, and parietal cortex; higher FDG uptake in the cingulate cortex, hippocampus, thalamus, and brainstem; reduced NFκB activity and iNOS expression; and increased enzymatic activity of CAT and SOD in some brain areas. Our study suggests that some schizophrenia-related IOS changes can be prevented in the MIS model. It also stresses the need to search for novel strategies based on anti-inflammatory compounds in risk populations at early stages in order to alter the course of the disease.

Repeated exposure to sucrose for procedural pain in mouse pups leads to long-term widespread brain alterations.

Oral sucrose is administered routinely to reduce pain of minor procedures in premature infants and is recommended as standard care in international guidelines. No human or animal studies on effects of early repeated sucrose exposure on long-term brain development have been done in the context of pain. We evaluated the effects of repeated neonatal sucrose treatment before an intervention on long-term brain structure in mouse pups. Neonatal C57Bl/6J mice (n = 109) were randomly assigned to one of 2 treatments (vehicle vs sucrose) and one of 3 interventions (handling, touch, or needle-prick). Mice received 10 interventions daily from postnatal day 1 to 6 (P1-6). A dose of vehicle or 24% sucrose was given orally 2 minutes before each intervention. At P85-95, brains were scanned using a multichannel 7.0 T MRI. Volumes of 159 independent brain regions were obtained. Early repetitive sucrose exposure in mice (after correcting for whole brain volume and multiple comparisons) lead to smaller white matter volumes in the corpus callosum, stria terminalis, and fimbria (P < 0.0001). Cortical and subcortical gray matter was also affected by sucrose with smaller volumes of hippocampus and cerebellum (P < 0.0001). These significant changes in adult brain were found irrespective of the type of intervention in the neonatal period. This study provides the first evidence of long-term adverse effects of repetitive sucrose exposure and raises concerns for the use of this standard pain management practice during a period of rapid brain development in very preterm infants.

SY07CONSEQUENCES OF ADOLESCENT ALCOHOL ABUSE: HUMAN AND ANIMAL STUDIESSY07-1PERSISTENT CHANGES IN ADULT BRAIN IN RAT MODELS OF ADOLESCENT ALCOHOL ABUSE

Adolescent Alcohol abuse is common and alters brain development leading to persistent changes in adult brain and behavior. Adolescent intermittent ethanol (AIE) treatment (5 gm/kg, i.g.; 2 days on/2 days off; P25-P55) of wistar rats was used to model adolescent drinking and assessed in adulthood. AIE increased …

Changes in adult brain and behavior caused by neonatal limbic damage: implications for the etiology of schizophrenia

We tested the hypothesis that limbic damage in early development can cause aberrant maturation of brain structures known to be abnormal in adult schizophrenics: the hippocampus, prefrontal cortex, ventricles, and forebrain dopamine systems. We measured brain morphology, locomotor response to apomorphine, and cognitive processes in adult rats which received electrolytic damage to amygdala or hippocampus 48 h after birth. The behavioral measurements involved tasks which depend upon the integrity of the hippocampus or prefrontal cortex, and a task sensitive to forebrain dopamine system activation. The tasks included place navigation, egocentric spatial ability, and apomorphine-induced locomotion. The rats with lesions showed poor performance on the place navigation and egocentric spatial tasks and more apomorphine-induced locomotion after puberty than the sham lesion group. Regardless of lesion location, the adult rats showed smaller amygdalae and hippocampi, and larger lateral ventricles. Analyzing the lesion and sham rats together, adult amygdala volume was found to be positively correlated with cerebral cortex, prefrontal cortex, and hippocampal volumes and place navigation performance, and was negatively correlated with lateral ventricle volume. This study contributes to our understanding of the pathogenesis of schizophrenia by showing that early damage to limbic structures produced behavioral, morphological, and neuropharmacological abnormalities related to pathology in adult schizophrenics.

Differential Seizure-Induced and Developmental Changes of Neurexin Expression

The neurexins are differentially expressed neuronal surface proteins. Each neurexin gene (I, II, and III) has two promoters giving α and β major isoforms, and alternative splicing generates further extensive diversity. Following kainate- and pentylenetetrazole-induced seizures, there were no specific changes of expression of neurexins I and III in rat brains, whereas neurexin II expression increased in the dentate gyrus of the hippocampus. Both major isoforms were induced, particularly neurexin IIα. No significant alteration of neurexin II RNA splicing was observed. During postnatal development, neurexin II expression peaked in 6- to 10-day-old animals, in contrast with that of neurexins I and III; while neurexin IIα expression was elevated, neurexin IIβ expression was constant. The data suggest differential functions of the three neurexins and of their α- and β-isoforms and implicate neurexin IIα in the establishment of functional neuronal circuitry in postnatal brain and activity-dependent changes in adult brain.