Exposure to environmentally relevant phthalate mixture during pregnancy alters the physical and hemato-biochemical parameters in Black Bengal goats.

Several environmental pollutants, mostly chemicals and plasticizers, have an effect on the reproduction of small ruminants, causing abortion, delayed estrus, and decreased fertility. Phthalates are common in our environment and have been identified as endocrine disrupting chemicals (EDCs). The research work investigated the impact of dietary exposure to a phthalate mixture on physical and hemato-biochemical parameters in pregnant Black Bengal (BB) goats. A total of 20 clinically healthy, 1-2 months pregnant, aged 6-8 months with a body weight of 10-12 kg BB goats were collected and divided into two (n = 10) groups. The treatment group received a standard goat ration with a combination of different phthalates mixture while the control group was provided the same ration with the vehicle of aphthalatemixture until parturition. The physical parameters were measured with appropriate tools and blood samples were collected for hemato-biochemical tests. The results showed that the physiological parameters (body condition score, respiration rate and heart rate) were significantly (P < 0.05) reduced in phthalate-exposed goats without altering rectal temperature and rumen motility. The hematological parameters: RBC count, WBC count, hemoglobin concentration, hematocrit values and RBC indices were significantly (P < 0.05) lower in phthalate-exposed goats. Phthalate-exposed BB goats had significantly (P < 0.05) higher neutrophil and lower lymphocyte counts. Serum glucose, total protein, albumin and total cholesterol levels were significantly (P < 0.05) lower in phthalate-exposed BB goats but higher the values of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and blood urea nitrogen (BUN) levels in treated BB goats. It may be concluded that exposure to a phthalate mixture during pregnancy alters the physical, hematological and biochemical parameters in BB goats.

PlexinA1-deficient mice exhibit decreased cell density and augmented oxidative stress in parvalbumin-expressing interneurons in the medial prefrontal cortex.

PlexinA1 (PlxnA1) is a transmembrane receptor for semaphorins (Semas), a large family of axonal guidance cues vital during neural development. PlxnA1 is expressed in embryonic interneurons, and PlxnA1 deletion in mice leads to less interneurons in the developing cortex. In addition, PlxnA1 has been identified as a schizophrenia susceptibility gene. In our previous study, PlxnA1 knockout (KO) mice under a BALB/cAJ genetic background exhibited significantly increased self-grooming and reduced prepulse inhibition, a reliable phenotype for investigating the neurobiology of schizophrenia. However, the mechanism underlying the abnormal behavior of PlxnA1 KO mice remains unclear. We first confirmed PlxnA1 mRNA expression in parvalbumin-expressing interneurons (PV cells) in the medial prefrontal cortex (mPFC) of adult mice. Immunohistochemical analysis (IHC) showed significantly decreased densities of both GABAergic neurons and PV cells in the mPFC of PlxnA1 KO mice compared with wild type mice (WT). PV cells were found to express molecule interacting with CasL 1 (MICAL1), an effector involved in Sema-Plxn signaling for axon guidance, suggesting MICAL1 and PlxnA1 co-expression in PV cells. Furthermore, IHC analysis of 8-oxo-dG, an oxidative stress marker, revealed significantly increased oxidative stress in PlxnA1-deficient PV cells compared with WT. Thus, increased oxidative stress and decreased PV cell density in the mPFC may determine the onset of PlxnA1 KO mice's abnormal behavior. Accordingly, deficient PlxnA1-mediated signaling may increase oxidative stress in PV cells, thereby disrupting PV-cell networks in the mPFC and causing abnormal behavior related to neuropsychiatric diseases.

PlexinA1 deficiency in BALB/cAJ mice leads to excessive self-grooming and reduced prepulse inhibition.

PlexinA1 (PlxnA1) is a transmembrane receptor for semaphorins, a large family of proteins that act as axonal guidance cues during nervous system development. However, there are limited studies on PlxnA1 function in neurobehavior. The present study examined if PlxnA1 deficiency leads to behavioral abnormalities in BALB/cAJ mice. PlxnA1 knockout (KO) mice were generated by homologous recombination and compared to wild type (WT) littermates on a comprehensive battery of behavioral tests, including open field assessment of spontaneous ambulation, state anxiety, and grooming, home cage grooming, the wire hang test of muscle strength, motor coordination on the rotarod task, working memory on the Y maze alternation task, cued and contextual fear conditioning, anxiety on the elevated plus maze, sociability to intruders, and sensory processing as measured by prepulse inhibition (PPI). Measures of motor performance, working memory, fear memory, and sociability did not differ significantly between genotypes, while PlxnA1 KO mice displayed excessive self-grooming, impaired PPI, and slightly lower anxiety. These results suggest a crucial role for PlxnA1 in the development and function of brain regions controlling self-grooming and sensory gating. PlxnA1 KO mice may be a valuable model to investigate the repetitive behaviors and information processing deficits characteristic of many neurodevelopmental and psychiatric disorders.