Decreased parvalbumin mRNA levels in cerebellar Purkinje cells in autism

• Published in: Autism research 2017-11, Vol.10 (11), p.1787-1796
• Main Authors: Soghomonian, Jean‐Jacques, Zhang, Kunzhong, Reprakash, Sujithra, Blatt, Gene J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Autism; Autism Spectrum Disorder - metabolism; Brain; Cadaver; Cerebellum; Cerebellum - metabolism; Cerebral cortex; Cognition; Female; Forensic science; GABA; Gene expression; Hemispheres; Histochemistry; Humans; Male; Memory; Neurons; Neuropathology; parvalbumin; Parvalbumins - metabolism; post‐mortem; Purkinje Cells - metabolism; RNA, Messenger - metabolism; Young Adult
• ISSN: 1939-3792; 1939-3806
• DOI: 10.1002/aur.1835

Recent neuropathology studies in human brains indicate that several areas of the prefrontal cortex have decreased numbers of parvalbumin interneurons or decreased parvalbumin expression in Autism Spectrum disorders (ASD) [Hashemi, Ariza, Rogers, Noctor, & Martinez‐Cerdeno, 2017; Zikopoulos & Barbas, ]. These data suggest that a deficit in parvalbumin may be a key neuropathology of ASD and contribute to altered GABAergic inhibition. However, it is unclear if a deficit in parvalbumin is a phenomenon that occurs in regions other than the cerebral cortex. The cerebellum is a major region where neuropathology was first detected in ASD over three decades ago [Bauman & Kemper, ]. In view of the documented association between parvalbumin‐expressing neurons and autism, the objective of the present study was to determine if parvalbumin gene expression is also altered in Purkinje neurons of the cerebellum. Radioisotopic in situ hybridization histochemistry was used on human tissue sections from control and ASD brains in order to detect and measure parvalbumin mRNA levels at the single cell level in Purkinje cells of Crus II of the lateral cerebellar hemispheres. Results indicate that parvalbumin mRNA levels are significantly lower in Purkinje cells in ASD compared to control brains. This decrease was not influenced by post‐mortem interval or age at death. This result indicates that decreased parvalbumin expression is a more widespread feature of ASD. We discuss how this decrease may be implicated in altered cerebellar output to the cerebral cortex and in key ASD symptoms. Autism Res 2017, 10: 1787–1796. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The cerebellum of the brain controls movement and cognition, including memory and language. This study investigated mechanisms of cerebellar function in Autism. Our hypothesis is that parvalbumin, a molecule that controls and coordinate many cellular brain functions, contributes to the excitatory/inhibitory imbalance in Autism. We report that parvalbumin expression is depressed in Purkinje cells of the cerebellum in autism. This finding contributes to elucidate the cellular and molecular underpinings of autism and should provide a direction for future therapies.