Synaptic contacts in schizophrenia: Studies using immunocytochemical identification of dopaminergic neurons

Abstract

Immunocytochemical identification of dopaminergic neurons was performed using an immunoperoxidase method employing antibodies to tyrosine hydroxylase. The ultrastructure of synaptic contacts on dopaminergic (tyrosine hydroxylase immunopositive (TP) cells) neurons was investigated in the substantia nigra in the brains of four patients with schizophrenia and three mentally healthy subjects (controls). The substantia nigra of schizophrenia patients differed from control material in showing the following changes in the ultrastructure of presynaptic terminals contacting TP neurons: reductions in the size of terminals with dense matrix and poorly distinguished vesicles; swelling of terminals with small numbers of vesicles displaced from the active zone of the synapse; hyperplasia of mitochondria in some presynaptic boutons; appearance of membranous lamellar structures within or adjacent to presynaptic boutons. These changes to terminals were located mostly on the distal (small and intermediate) TP dendrites in the compact zone of the substantia nigra, where nearly all the dendrites detected belonged to dopaminergic neurons and the altered terminals formed asymmetrical contacts with short active zones. In the reticular part of the substantia nigra of schizophrenic patients, changes in the ultrastructure of presynaptic terminals were relatively rare; altered terminals contacted both tyrosine hydroxylase immunopositive as well as with the tyrosine hydroxylase immunonegative dendrites located in this structure.

Sex and laterality differences in parkinsonian impairment and transcranial ultrasound in never-treated schizophrenics and their first degree relatives in an Andean population

“…Motor impairment was consistently also worse (and more asymmetric) in males. A number of additional observations argue in favor of a loss of dopaminergic neuronal function in schizophrenia (Finlay, 2001;Masciotra et al, 2005): eurons in the ventral tegmental area appear dystrophic and may be reduced in number (Bogerts et al, 1983;Kolomeets and Uranova, 1999). …”

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders

“…In detail, ultrastructural alterations encompassing reduction and swelling of DA terminals, mitochondrial alterations, and multi-lamellar structures were reported within DA terminals of the SNpc [168]. Interestingly, these ultrastructural abnormalities are highly reminiscent of those induced by METH.…”

Postmortem studies on mitochondria in schizophrenia

“…At the ultrastructural level, mitochondrial hyperplasia has been observed within axon terminals that synapse onto dopamine neurons in the SN (Kolomeets and Uranova, 1999). However, mitochondria in dopamine neuronal somata were similar in size and structural integrity between SZ and NCs (Walker and Roberts, 2016).…”

“…mtDNA, mitochondrial DNA. 1) Roberts et al, 2015; 2) Barksdale, et al, 2014; 3) Wang et al, 1999; 4) Reid et al, 2010; 5) Uranova et al, 2007, Vikhreva et al, 2016; 6) Mamdani et al, 2014; 7) Somerville et al, 2011; 8) Somerville et al, 2012; 9) Maurer et al, 2001; Ben-Shakar & Karry, 2008; 10) Cavalier et al, 1995; Prince et al, 1999, 2000; 11) Uranova et al, 1996, 2001; 12) Kung & Roberts, 1999; 13) McCollum et al, 2015; 14) Kolomeets & Uranova, 1999; 15) Walker & Roberts, 2016; 16) Rice et al, 2014.…”