section of hippocampus showing a GABAergic neuron.
Parvalbumin and cresyl
violet stain. Magnification 60 times.
The biology of brain development and psychiatric disorders
Preterm birth is associated with an increased risk of brain injury,
persistently smaller brain volume and cognitive deficits. However, the
relationship between these abnormalities and structural, as well as molecular
changes and functions, remains elusive. Using design based stereological methods
and a well-established pig model we will evaluate the effect of preterm birth on
brain parameters such as regional volumes and surface areas.
Dopamine 2 receptor (DRD2) is of major interest to the pathophysiology of
schizophrenia both as a target for antipsychotic drug action as well as a
schizophrenia-associated risk gene. The dopamine 1 receptor (DRD1) is thought to
mediate some of the cognitive deficits in schizophrenia, including impairment of
working memory that relies on normal dorsolateral prefrontal cortex (DLPFC)
function. To better understand the association of dopamine receptors with
schizophrenia, we studied the expression of three DRD2 splice variants and the
DRD1 transcript in DLPFC, hippocampus and caudate nucleus in a large cohort of
subjects, including patients with schizophrenia, affective disorders and
non-psychiatric controls, and examined genotype-expression associations of 278
SNPs located in or near DRD2 and DRD1 genes.
Accepted for publications in
Molecular Psychiatry, 2013
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
toreduced 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).
Published in J. Neurochem. (2013) Feb;
1. Karlsen,A.S., Kaalund,S.S., Moller,M., Plath,N., & Pakkenberg,B.
Expression of presynaptic markers in a neurodevelopmental animal model with
relevance to schizophrenia. Neuroreport 24, 928-933
2. Kaalund,S.S. et al. Differential expression of
parvalbumin in neonatal phencyclidine-treated rats and socially isolated rats.
J. Neurochem. 124, 548-557 (2013).
3. Kaalund S.S. et al. Contrasting Changes in DRD1 and
DRD2 Splice Variant Expression in Schizophrenia and Affective Disorders,
and Associations with SNPs in Postmortem Brain. [Accepted for publication in
4. Kaalund,S.S. et al. Investigation of 4q-deletion in two unrelated
patients using array CGH. Am. J. Med. Genet. A 146A, 2431-2434