Exercise has been shown to be beneficial for Parkinson’s disease (PD). A major interest in our lab has been to investigate how exercise modulates basal ganglia function and modifies disease progression. Dopamine (DA) depletion leads to loss of dendritic spines within the caudate nucleus and putamen (striatum) in PD and its animal models and contributes to motor impairments. Striatal medium spiny neurons (MSNs) can be delineated into two populations, the dopamine D1 receptor (DA-D1R)-containing MSNs of the direct pathway and dopamine D2 receptor (DA-D2R)-containing MSNs of the indirect pathway. There is evidence to suggest that the DA-D2R-indirect pathway MSNs may be preferentially affected after DA-depletion with a predominate loss of dendritic spine density when compared to MSNs of the DA-D1R-direct pathway in rodents; however, others have reported that both pathways may be affected in primates. The purpose of this study was to investigate the effects of intensive exercise on dendritic spine density and arborization in MSNs of these two pathways in the MPTP mouse model of PD. We found that MPTP led to a decrease in dendritic spine density in both DA-D1R-and DA-D2R-containing MSNs and 30 days of intensive treadmill exercise led to increased dendritic spine density and arborization in MSNs of both pathways. In addition, exercise increased the expression of synaptic proteins PSD-95 and synaptophysin. Taken together these findings support the potential effect of exercise in modifying synaptic connectivity within the DA-depleted striatum and in modifying disease progression in individuals with PD.

Postnatal ID in piglets affects brain development, especially white matter. If the effects of ID persist, it might explain the lasting detrimental effects on cognition.

Maternal infections during pregnancy are associated with increased risk of neurodevelopmental disorders, although the precise mechanisms remain to be elucidated. Previously, we established a maternal immune activation (MIA) model using swine, which results in altered social behaviors of piglet offspring. These behavioral abnormalities occurred in the absence of microglia priming. Thus, we examined fetal microglial activity during prenatal development in response to maternal infection with live porcine reproductive and respiratory syndrome virus. Fetuses were obtained by cesarean sections performed 7 and 21 d postinoculation (dpi). MIA fetuses had reduced brain weights at 21 dpi compared to controls. Furthermore, MIA microglia increased expression of major histocompatibility complex class II that was coupled with reduced phagocytic and chemotactic activity compared to controls. High-throughput gene-expression analysis of microglial-enriched genes involved in neurodevelopment, the microglia sensome, and inflammation revealed differential regulation in primary microglia and in whole amygdala tissue. Microglia density was increased in the fetal amygdala at 7 dpi. Our data also reveal widespread sexual dimorphisms in microglial gene expression and demonstrate that the consequences of MIA are sex dependent. Overall, these results indicate that fetal microglia are significantly altered by maternal viral infection, presenting a potential mechanism through which MIA impacts prenatal brain development and function. maternal immune activation | microglia | neurodevelopment | prenatal inflammation | pig Author contributions: A.M.A., M.A.L., and R.W.J. designed research; A.M.A., M.A.L., M.P.C., S.M.M., and B.J.L. performed research; A.M.A., M.P.C., and S.M.M. analyzed data; A.M.A., M.A.L., and R.W.J. interpreted data; and A.M.A. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission.Published under the PNAS license. NEUROSCIENCEDownloaded by guest on July 10, 2020 3 symbols = P < 0.001, 2 symbols = P < 0.01, and 1 symbol = P < 0.05.Antonson et al.

Background: Intrauterine growth restriction is a common cause of small for gestational age (SGA) infants worldwide. SGA infants are deficient in digestive enzymes required for fat digestion and absorption compared to appropriate for gestational age (AGA) infants, putting them at risk for impaired neurocognitive development.on reversal day 2. HF increased arachidonic acid (ARA) percentage in the cerebellum and total ARA in the hippocampus.Conclusions: HF enhanced brain development in the neonatal piglet measured by brain volume and WM volume in specific brain regions; however, more studies are needed to assess long-term outcomes.

During the postnatal period the developing brain is vulnerable to insults including nutrient insufficiency and infection that may lead to disrupted development and cognitive dysfunction. Since iron deficiency (ID) often presents with immunodeficiency, the objective of this study was to investigate peripheral viremia and inflammation as well as brain microglial phenotype and function when ID and respiratory infection occur simultaneously in a neonatal piglet model. On postnatal day 2 (PD 2) male and female piglets were assigned to one of four treatments and fed either control or ID milk replacer. On PD 8 half the pigs on each diet were inoculated with either vehicle or porcine reproductive and respiratory syndrome virus (PRRSV; P-129). Blood samples were collected prior to inoculation (PD 7) and repeated once weekly. Rectal temperature, feeding score, and sickness behavior were measured daily until PD 28. Hematocrit, hemoglobin, and serum iron were reduced by ID but not PRRSV infection. PRRSV-infected piglets displayed viremia by PD 14; however, those fed control diet had lower viral titer on PD 28, while circulating virus remained elevated in those fed an ID diet, suggesting that ID either impaired immune function necessary for viral clearance or increased viral replication. ID piglets infected with PRRSV displayed reduced sickness behavior compared to those fed control diet on PD 13-15 and 18-20. While ID piglet sickness behavior progressively worsened, piglets fed control diet displayed improved sickness score after PD 21. Microglia isolated from PRRSV piglets had increased MHCII expression and phagocytic activity ex vivo compared to uninfected piglets. ID did not alter microglial activation or phagocytic activity. Similarly, microglial cytokine expression was increased by PRRSV but unaffected by ID, in stark contrast to peripheral blood mononuclear cell (PBMC) cytokine expression, which was increased by infection and generally decreased by ID. Taken together, these data suggest that ID decreases peripheral immune function leading to increased viremia, but immune activity in the brain is protected from acute ID.