Title: Activation of nicotinic alpha(7) acetylcholine receptor enhances long term potentation in wild type mice but not in APP(swe)/PS1DeltaE9 mice Soderman A, Mikkelsen JD, West MJ, Christensen DZ, Jensen MS Ref: Neuroscience Letters, 487:325, 2011 : PubMed
Amyloid beta (Abeta) plays a central role in Alzheimer's disease (AD) and binds to the nicotinic alpha(7) receptor (alpha(7) nAChR). Little is known about the degree to which the binding of Abeta to the alpha(7) nAChR influences the role of this receptor in long-term potentiation (LTP), however. We have studied the effect of the partial alpha(7) nAChR agonist SSR180711 on hippocampal slice preparations from normal wild type (Wt) and APP(swe)/PS1DeltaE9 transgenic (Tg) mice. In the hippocampal slices from the 6 months old Wt mice, the application of both nicotine (5muM) and SSR180711 (300nM) resulted in a significant enhancement of LTP expressed in area CA1. However, in the Tg mice the application of SSR180711 did not result in an increase in LTP beyond control levels. The amount of binding of the alpha(7) nAChR ligand 125-I-alpha-bungarotoxin was not different between in Tg and Wt mice. These findings indicate that the alpha(7) nAChR is functionally blocked in the hippocampal neurons, downstream of the alpha(7) nAChR, and that this is likely due to an interaction between the receptor and Abeta, which leads to changes in LTP.
Title: The anatomy of the porcine subthalamic nucleus evaluated with immunohistochemistry and design-based stereology Larsen M, Bjarkam CR, Ostergaard K, West MJ, Sorensen JC Ref: Anatomy & Embryology (Berl), 208:239, 2004 : PubMed
This study provides a light-microscopic description of the organization, morphology and number of neurons in the subthalamic nucleus (STN) of the Gottingen minipig. It is based on histological material stained with Nissl, Golgi and autometallographic techniques, and employs design-based stereological estimation of the total neuron number. The organization of several neurotransmitters in the STN has been evaluated in histological preparations stained for acetylcholinesterase (AChE) and immunostained for choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD) and glutamate. In all of the stained preparations the STN appeared as a distinct lens-shaped structure located in the caudal diencephalon, medial to the internal capsule and ventrolateral to the zona incerta. Rostrally, the STN approached the globus pallidus pars interna, whereas caudally the ventromedial part of the STN was adjacent to the rostral part of the substantia nigra pars compacta (SNc), where some of the neurons of the two nuclei merged. The neurons in the STN had medium-sized (25-40 microm) ovoid or fusiform cell bodies, from which three to six large dendrites emanated in a direction predominantly parallel to the long axis of the STN. Immunohistochemistry revealed that most of the subthalamic neurons were glutamatergic and differed significantly in appearance from the large stellate TH-positive cells of the adjacent SNc. Numerous TH-positive bouton-rich fibers traversed the STN. The GAD-staining revealed a large number of terminals within the boundaries of the STN. The STN was highly AChE-positive, reflecting a prominent innervation by ChAT-positive terminals. The total number of subthalamic neurons in one hemisphere was estimated to be approximately 56,000. We conclude that the neuroarchitecture of the porcine STN is similar to primates, including humans, and appears well-suited for further studies examining the role of the STN in movement disorders.
Our understanding of the genes involved in Alzheimer's disease (AD) is incomplete. Using subtractive cloning technology, we discovered that the alpha/beta-hydrolase fold protein gene NDRG2 (NDRG family member 2) is upregulated at both the RNA and protein levels in AD brains. Expression of NDRG2 in affected brains was revealed in (1) cortical pyramidal neurons, (2) senile plaques and (3) cellular processes of dystrophic neurons. Overexpression of two splice variants encoding a long and short NDRG2 isoform in hippocampal pyramidal neurons of transgenic mice resulted in localization of both isoforms to dendritic processes. Taken together, our findings suggest that NDRG2 upregulation is associated with disease pathogenesis in the human brain and provide new insight into the molecular changes that occur in AD.
