Differential expression of parvalbumin in neonatal phencyclidine‐treated rats and socially isolated rats

Abstract

Decreased parvalbumin expression is a hallmark of the pathophysiology of schizophrenia and has been associated with abnormal cognitive processing and decreased network specificity. It is not known whether this decrease is due to reduced expression of the parvalbumin protein or degeneration of parvalbumin-positive interneurons (PV + interneurons). In this study, we examined PV + expression in two rat models of cognitive dysfunction in schizophrenia: the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical fractionator, we counted neurons, PV + interneurons, and glial cells in the medial prefrontal cortex (mPFC) and hippocampus (HPC). In addition, we quantified the mRNA level of parvalbumin in the mPFC. There was a statistically significant reduction in the number of PV + interneurons (p = 0.021) and glial cells (p = 0.024) in the mPFC of neonatal phencyclidine rats, but not in SI rats. We observed no alterations in the total number of neurons, hippocampal PV + interneurons, parvalbumin mRNA expression or volume of the mPFC or HPC in the two models. Thus, as the total number of neurons remains unchanged following phencyclidine (PCP) treatment, we suggest that the decreased number of counted PV + interneurons represents a reduced parvalbumin protein expression below immunohistochemical detection limit rather than a true cell loss. Furthermore, these results indicate that the effect of neonatal PCP treatment is not limited to neuronal populations.

Role of mGlu5 Receptors and Inhibitory Neurotransmission in M1 Dependent Muscarinic LTD in the Prefrontal Cortex: Implications in Schizophrenia

“…Interestingly, transient PCP treatment at this developmental stage results in a sustained loss of GABAergic inhibition in the PFC, 48,49 a selective loss of a specific subpopulation of inhibitory interneurons that express parvalbumin, 50,51 and a shift in excitatory/inhibitory balance. 32,52,53 This is important since loss of interneurons or inhibitory function is a hallmark in schizophrenia pathology and this interneurons dysfunction could underlie many of the cognitive symptoms of schizophrenia.…”

Subchronic phencyclidine treatment in adult mice increases GABAergic transmission and LTP threshold in the hippocampus

“…In animal models too, including the scPCP model, it has been reported that there is reduced parvalbumin expression in the cortex and the hippocampus (Abdul-Monim et al, 2007; Behrens et al, 2008; Jenkins et al, 2010; McKibben et al, 2010; Wang et al, 2008). More recently, it has been demonstrated that postnatal administration of PCP in rodents causes a reduction in expression of parvalbumin protein without a reduction in the number of interneurons (Kaalund et al, 2013; Powell et al, 2012). Furthermore, an elevated density of cFOS positive interneurons in the hippocampus after repeated NMDA receptor antagonist treatment suggests that there is increased activity of hippocampal interneurons in these models (Bird et al, 1978; Keilhoff et al, 2004; Kjaerby et al, 2013).…”

Impact of Ketamine on Neuronal Network Dynamics: Translational Modeling of Schizophrenia‐Relevant Deficits

“…They depend on a functioning network of fast-firing interneurons that show structural abnormalities in human postmortem brains [84][85][86][87][88] of schizophrenics, suggesting that impaired neuronal oscillations serve as a mechanistic link between deficiencies of the interneuron network and cognitive dysfunction. Developmental abnormalities of parvalbumin-positive interneurons are consistently observed in chronic animal models produced by a variety of techniques [27,[89][90][91][92][93][94][95][96][97], and in the past several years, it has also been firmly established that the essential features of human schizophrenia recapitulated by rodent models include abnormal oscillations in low-(delta, theta) and in the high-(beta, gamma)frequency bands [25][26][27]48,89,[98][99][100][101][102][103][104][105][106][107][108][109][110][111].…”