Parvalbumin interneuron deficiency in the prefrontal and motor cortices of spontaneously hypertensive rats: an attention-deficit hyperactivity disorder animal model insight

Ewelina Bogdańska-Chomczyk; Maciej Równiak; Andrew Chih-Wei Huang; Anna Kozłowska

doi:10.3389/fpsyt.2024.1359237

Parvalbumin interneuron deficiency in the prefrontal and motor cortices of spontaneously hypertensive rats: an attention-deficit hyperactivity disorder animal model insight

Front Psychiatry. 2024 Mar 27:15:1359237. doi: 10.3389/fpsyt.2024.1359237. eCollection 2024.

Authors

Ewelina Bogdańska-Chomczyk¹, Maciej Równiak², Andrew Chih-Wei Huang³, Anna Kozłowska¹

Affiliations

¹ Department of Human Physiology and Pathophysiology, School of Medicine, University of Warmia and Mazury, Olsztyn, Poland.
² Department of Animal Anatomy and Physiology, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Olsztyn, Poland.
³ Department of Psychology, Fo Guang University, Yilan County, Taiwan.

Abstract

Background: Attention deficit hyperactivity disorder (ADHD) is characterized by impairments in developmental-behavioral inhibition, resulting in impulsivity and hyperactivity. Recent research has underscored cortical inhibition deficiencies in ADHD via the gamma-aminobutyric acid (GABA)ergic system, which is crucial for maintaining excitatory-inhibitory balance in the brain. This study explored postnatal changes in parvalbumin (PV) immunoreactivity, indicating GABAergic interneuron types, in the prefrontal (PFC) and motor (MC) cortices of spontaneously hypertensive rats (SHRs), an ADHD animal model.

Methods: Examining PV- positive (PV+) cells associated with dopamine D2 receptors (D2) and the impact of dopamine on GABA synthesis, we also investigated changes in the immunoreactivity of D2 and tyrosine hydroxylase (TH). Brain sections from 4- to 10-week-old SHRs and Wistar Kyoto rats (WKYs) were immunohistochemically analyzed, comparing PV+, D2+ cells, and TH+ fiber densities across age-matched SHRs and WKYs in specific PFC/MC regions.

Results: The results revealed significantly reduced PV+ cell density in SHRs: prelimbic (~20% less), anterior cingulate (~15% less), primary (~15% less), and secondary motor (~17% less) cortices. PV+ deficits coincided with the upregulation of D2 in prepubertal SHRs and the downregulation of TH predominantly in pubertal/postpubertal SHRs.

Conclusion: Reduced PV+ cells in various PFC regions could contribute to inattention/behavioral alterations in ADHD, while MC deficits could manifest as motor hyperactivity. D2 upregulation and TH deficits may impact GABA synthesis, exacerbating behavioral deficits in ADHD. These findings not only shed new light on ADHD pathophysiology but also pave the way for future research endeavors.

Keywords: GABAergic system; animal model; attention-deficit/hyperactivity disorder; cortex; dopamine receptor; parvalbumin; spontaneously hypertensive rat; tyrosine hydroxylase.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work was supported by grant No. PL-TW II/4/2015 from the National Centre for Research and Development in Poland. Funded by The Minister of Science under “The Regional Initiative of Excellence Program”.