Neuroscience Letters 411 (2007) 123–127 Immunoreactivity of 43 kDa growth-associated protein is decreased in post mortem hippocampus of bipolar disorder and schizophrenia Simon Y. Tian a,b , Jun-Feng Wang a,b,c , Yarema B. Bezchlibnyk a , L. Trevor Young a,b,c,∗ a The Vivian Rakoff Mood Disorders Laboratory, Centre for Addiction and Mental Health, Toronto, Ont., Canada b Department of Psychiatry, University of Toronto, Toronto, Ont., Canada c Institute of Medical Science, University of Toronto, Toronto, Ont., Canada Received 19 June 2006; received in revised form 27 September 2006; accepted 18 October 2006 Abstract Impairment of neuroplasticity is considered to play a role in the pathogenesis of psychiatric disorders. To further characterize the impairment of neuroplasticity in psychiatric disorders, expression of the neuronal plasticity marker 43 kDa growth-associated protein (GAP-43) was detected in postmortem hippocampal sub-regions from psychiatric patients including major depressive disorder, bipolar disorder and schizophrenia subjects, and matched control subjects. We found that GAP-43 protein levels in the hippocampal hilar region were significantly lower in bipolar disorder and schizophrenia subjects than in control subjects. We also found that GAP-43 protein levels in the inner molecular layer of the dentate gyrus and the stratum radiatum of CA2 region were reduced in a trend in bipolar disorder and schizophrenia subjects when compared with control subjects. These results suggest that impairment of neuroplasticity may occur in the hippocampus of bipolar disorder and schizophrenia patients. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Postmortem hippocampus; 43 kDa growth-associated protein; Neuroplasticity; Immunohistochemistry; Bipolar disorder; Schizophrenia A growing body of data from neuroimaging and neuropatholog- ical studies indicates reduced brain volume and cell loss in mood disorders including bipolar disorder (BD) and major depressive disorder (MDD) as well as in schizophrenia (SCZ) [5,28]. Much evidence also suggests that mood disorders and SCZ may share some genetic substrates and have overlapping pathological fea- tures in key brain regions [1,24,27]. Long-term adaptation and neuronal resilience are critical to maintaining cellular plasticity in brain regions and it is increasingly recognized that impairment of these processes may play an important role in the pathogen- esis of these psychiatric disorders [19,24]. The hippocampus is a medial temporal structure involved in mood regulation that is susceptible to damage during chronic stress [20,25]. Recent studies of patients with mood disor- ders have revealed cellular damage and volumetric changes in this brain region [5]. Studies in the hippocampus also suggest that mood stabilizing drugs produce neuroprotective and neu- ∗ Corresponding author at: Centre for Addiction and Mental Health, 250 Col- lege Street, Room 814, Toronto, Ont. M5T 1R8, Canada. Tel.: +1 416 979 4749; fax: +1 416 260 4189. E-mail address: trevor young@camh.net (L.T. Young). rotrophic effects in the treatment of BD, and that early and aggressive treatment with mood stabilizing drugs may prevent some of the deleterious long-term structural brain changes asso- ciated with BD [19,30–32]. One broadly studied marker of neuronal plasticity is the 43 kDa growth-associated protein (GAP-43), which is critical to proper regulation of neuronal morphology and communication [3,8,21,22]. This neuron-specific protein, located in the nerve terminal, is induced in adults by axonal injury and plays critical roles in neuronal sprouting, synaptic reorganization and alter- ation of neuronal morphology [3]. Eastwood and Harrison [12] have found, using immunoblotting analysis, that GAP-43 were reduced in post mortem cingulate cortex of BD. GAP-43 has been found to be increased by antidepressant treatment in our laboratory, and has also been shown to be associated with depres- sion and suicide in the cerebral cortex [8,15]. To investigate changes of neuroplasticity in the hippocampus of psychiatric disorders, in the present study we measured GAP-43 protein levels in CA1, CA3 and dentate gyrus regions of postmortem hippocampal sections from subjects with MDD, BD, SCZ and non-neurological, non-psychiatric controls. The postmortem brain tissue used in the present study was generously provided by the Stanley Neuropathology Consor- 0304-3940/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2006.10.031