Studies suggest age- and sex-dependent structural and functional patterns of human cerebral lateralization underlie hemisphere specialization and its alterations in schizophrenia. Recent works report sexual dimorphism of neurons in the hippocampal formation and specialization of hemispheres in rats. Our experiments indicate for the first time functional lateralization of the high-affinity choline uptake (HACU) system directly associated with a synthesis of acetylcholine in the hippocampus of Wistar rats. The markedly increased HACU activity was found in the left compared to the right hippocampus of adult male but not female animals. Lineweaver-Burk plot analysis revealed a statistically significant increase of Vmax in the left hippocampus of 14-day-old when compared to 7-day-old males. It appears that laterality of HACU occurs during late postnatal maturation, and its degree is markedly enhanced after puberty and attenuated during aging. Quinolinic acid (QUIN), an endogenous agonist of N-methyl-D-aspartate type glutamate receptors, was used in this study to evaluate the neurodevelopmental hypothesis of schizophrenia. It is known that elevated levels of QUIN accompany viral infections, increasing the risk of developing schizophrenia. Bilateral intracerebroventricular application of QUIN (250 nmoles/ventricle) to pups aged 12 days significantly impaired the cholinergic hippocampal system of adolescent male and female rats and reversed lateralization of male HACU. Morphological analysis indicated marked changes in brain lesion sizes (extensive 24 h and moderate 38 days after the operation). Asymmetry of lesions was observed in the majority of cases, but the left hemisphere was not generally more vulnerable to QUIN effects than the right side. Moreover, no lateral differences were found between lesioned hippocampi in the specific binding of [3H]hemicholinium-3 (10%-15% loss of binding sites when compared to sham-operated animals). In summary, our results indicate a symmetrical drop in the number of choline carriers of lesioned male rats but a asymmetrical decrease in the activity of remaing carriers, suggesting defects in processes of sexual brain differentiation, leading under normal conditions to the higher activity of carriers in the left hippocampus. The data demonstrate viral infection-mediated alterations in normal patterns of brain asymmetry and are discussed in relation to animal models of neurodevelopmental and neurodegenerative diseases.

Prague Psychiatric Centre Prague Czech Republic

Zobrazit více v PubMed

Neurosci Lett. 1990 Oct 2;118(1):128-31 PubMed

Neuropsychopharmacology. 2000 Sep;23(3):223-39 PubMed

J Appl Toxicol. 2002 Mar-Apr;22(2):129-37 PubMed

Neurobiol Aging. 2002 Jan-Feb;23(1):87-95 PubMed

Brain Res. 1998 Feb 23;785(1):167-70 PubMed

J Neurochem. 1985 Jan;44(1):11-24 PubMed

Psychoneuroendocrinology. 1991;16(1-3):121-9 PubMed

Can J Physiol Pharmacol. 1994 Dec;72(12):1473-82 PubMed

J Neurochem. 1976 May;26(5):909-22 PubMed

Neuropharmacology. 1996 Apr;35(4):449-58 PubMed

Neuroscience. 2000;101(4):931-8 PubMed

Biol Psychiatry. 1999 Feb 15;45(4):395-402 PubMed

Arch Neurol. 1985 May;42(5):428-59 PubMed

Trends Neurosci. 1999 Feb;22(2):67-74 PubMed

Front Neuroendocrinol. 1998 Oct;19(4):323-62 PubMed

Curr Opin Neurobiol. 1997 Apr;7(2):285-9 PubMed

Neurosci Biobehav Rev. 1996 Winter;20(4):607-15 PubMed

Nat Rev Neurosci. 2003 Jan;4(1):37-48 PubMed

Br J Psychiatry Suppl. 1999;(37):7-11 PubMed

Brain Res. 1987 Jul;431(1):156-60 PubMed

Arch Gerontol Geriatr. 1993 Nov-Dec;17(3):179-88 PubMed

Int J Psychophysiol. 1998 Jan;28(1):37-62 PubMed

Neurochem Res. 2001 Mar;26(3):203-12 PubMed

Neurochem Res. 2003 Apr;28(3-4):397-405 PubMed

Neuroscience. 1991;42(2):379-85 PubMed

Anal Biochem. 1976 May 7;72:248-54 PubMed

Arch Gen Psychiatry. 1996 Jul;53(7):585-94 PubMed

Exp Gerontol. 1995 Mar-Apr;30(2):125-36 PubMed

Biol Psychiatry. 1995 Jul 1;38(1):22-33 PubMed

Brain Res Bull. 2000 Nov 1;53(4):415-20 PubMed

Psychoneuroendocrinology. 1998 Jul;23(5):519-47 PubMed

Brain Res Brain Res Rev. 1999 Aug;30(2):135-52 PubMed

Neuroreport. 2001 Oct 8;12(14):3019-22 PubMed

Epilepsia. 1999 Apr;40(4):414-23 PubMed

Acute and Chronic Sleep Deprivation-Related Changes in N-methyl-D-aspartate Receptor-Nitric Oxide Signalling in the Rat Cerebral Cortex with Reference to Aging and Brain Lateralization

A Rat Model of Alzheimer's Disease Based on Abeta42 and Pro-oxidative Substances Exhibits Cognitive Deficit and Alterations in Glutamatergic and Cholinergic Neurotransmitter Systems

N-Methyl-d-Aspartate Receptor - Nitric Oxide Synthase Pathway in the Cortex of Nogo-A-Deficient Rats in Relation to Brain Laterality and Schizophrenia

Aging and lateralization of the rat brain on a biochemical level

Sex-dependent actions of amyloid beta peptides on hippocampal choline carriers of postnatal rats

Exposure of postnatal rats to a static magnetic field of 0.14 T influences functional laterality of the hippocampal high-affinity choline uptake system in adulthood; in vitro test with magnetic nanoparticles