Responses in the aged rat brain after total immunolesion

Z, Gu; Yu, Juan; Perez‐Polo, J. Regino

doi:10.1002/(sici)1097-4547(19981001)54:1<7::aid-jnr2>3.0.co;2-m

Cited by 26 publications

(21 citation statements)

References 49 publications

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“…We were not concerned about the loss of GABAergic neurons by the toxin because intact GABA A receptormediated inhibition is not required for mLTD expression (see Fig. 1 I), and several studies report that GABAergic neurons are mostly spared at concentrations close to or higher than those used in the current study (Berger-Sweeney et al, 1994;Heckers et al, 1994;Hortnagl and Hellweg, 1997;Gu et al, 1998;McGaughy et al, 2002). Superior cervical ganglionectomies were performed via a neck incision to expose the carotid arteries, followed by visualization and bilateral removal of the ganglia.…”

Section: Methodsmentioning

confidence: 99%

Sympathetic Sprouting Drives Hippocampal Cholinergic Reinnervation That Prevents Loss of a Muscarinic Receptor-Dependent Long-Term Depression at CA3–CA1 Synapses

Scheiderer

McCutchen²,

Thacker³

et al. 2006

J. Neurosci.

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Degeneration of septohippocampal cholinergic neurons results in memory deficits attributable to loss of cholinergic modulation of hippocampal synaptic circuits. A remarkable consequence of cholinergic degeneration is the sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. The functional impact of sympathetic ingrowth on synaptic physiology has never been investigated. Here, we report that, at CA3-CA1 synapses, a Hebbian form of long-term depression (LTD) induced by muscarinic M 1 receptor activation (mLTD) is lost after medial septal lesion. Unexpectedly, expression of mLTD is rescued by sympathetic sprouting. These effects are specific because LTP and other forms of LTD are unaffected. The rescue of mLTD expression is coupled temporally with the reappearance of cholinergic fibers in hippocampus, as assessed by the immunostaining of fibers for VAChT (vesicular acetylcholine transporter). Both the cholinergic reinnervation and mLTD rescue are prevented by bilateral superior cervical ganglionectomy, which also prevents the noradrenergic sympathetic sprouting. The new cholinergic fibers likely originate from the superior cervical ganglia because unilateral ganglionectomy, performed when cholinergic reinnervation is well established, removes the reinnervation on the ipsilateral side. Thus, the temporal coupling of the cholinergic reinnervation with mLTD rescue, together with the absence of reinnervation and mLTD expression after ganglionectomy, demonstrate that the autonomic-driven cholinergic reinnervation is essential for maintaining mLTD after central cholinergic cell death. We have discovered a novel phenomenon whereby the autonomic and central nervous systems experience structural rearrangement to replace lost cholinergic innervation in hippocampus, with the consequence of preserving a form of LTD that would otherwise be lost as a result of cholinergic degeneration.

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Section: Methodsmentioning

confidence: 99%

Sympathetic Sprouting Drives Hippocampal Cholinergic Reinnervation That Prevents Loss of a Muscarinic Receptor-Dependent Long-Term Depression at CA3–CA1 Synapses

Scheiderer

McCutchen²,

Thacker³

et al. 2006

J. Neurosci.

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“…Interestingly, all of these neurotrophins are increased following treatment with nicotine (Belluardo et al, 1998;Maggio et al, 1998;Kenny et al, 2000;Martinez-Rodriguez et ah, 2003) and Maggio et al (1998) found that the beneficial effects of nicotine in the Parkinson's disease mouse model were correlated with increases in FGF-2 and BDNF. There are no changes in basal levels of hippocampal BDNF or NGF mRNA one to four weeks after cholinergic depletion in rats (Yu et al, 1995;Gu et al, 1998), but at later time points significant decreases were reported in the hippocampus and cortical areas (Kokaia et al, 1996;Ferencz et al, 1997). Interestingly, this depletion also eliminated the seizure mediated increase in BDNF and NGF suggesting a role for acetylcholine in mediating the endogenous response of neurotrophins to injury (Kokaia et al, 1996;Ferencz et al, 1997).…”

Section: Effects O F Ach On Neurotrophin Expression and Neurogenesismentioning

confidence: 96%

Revisiting the cholinergic hypothesis in the development of Alzheimer's disease

Craig

Hong

McDonald

2011

Neuroscience & Biobehavioral Reviews

402

263

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Alzheimer's disease (AD) is the most common form of dementia affecting the elderly population today; however, there is currently no accurate description of the etiology of this devastating disorder. No single factor theory has been demonstrated as being causative; however, an alternative theory suggests that the interaction of multiple risk factors is responsible for AD. In this thesis I present data suggesting a neuroprotective role for acetylcholine during aging. Using a rat model of cholinergic depletion of the medial septum, I explored the effects of four common risk factors for AD (stress, seizures, stroke and circadian dysfunction) targeted at the hippocampus and examined the effects on measures of hippocampal dependent (water maze) and hippocampal independent (fear conditioning) memory. Here, I propose a role for acetylcholinemediated compensatory mechanisms in the functional recovery observed following sub threshold insults similar to those commonly observed in the elderly. m First and foremost I would like to thank my supervisor, Dr. Robert McDonald. Thank you for your support and encouragement, and for allowing me the independence to pursue my own projects and to learn from my experiences. I would also like to thank Nhung Hong for doing the majority of the cholinergic depletion and stroke surgeries used in this thesis and for teaching me the techniques. I would like to give a huge thank you to Joelle Kopp who was an invaluable asset who assisted in histology and spent many hours on the microscope counting cholinergic neurons. I would also like to thank Dr. Christine Werk for patiently reading and re-reading early drafts of my papers and this thesis and Dr.Hugo Lehmann for all his help in running statistics and interpreting my data. In addition, many thanks go out to Courtney Lamb, Robert Court and Arthur Verhoef for helping me with histology and behavioural testing, to Keri Colwell for running the corticosterone assays, the Metz lab for kindly allowing me the use of their microscope and to Karen Dow-Cazel and the rest of the animal care staff for taking care of my rats and helping me set up the circadian experiements. The cholinergic hypothesis of Alzheimer's disease 6 Acknowledgements IVThe basal forebrain cholinergic system 8The role of the basal forebrain cholinergic system in learning and memory 10The current state of the cholinergic hypothesis of Alzhimer's disease 15Risk factors for Alzheimer's disease 16Multiple combinations of co-factors theory of Alzheimer's disease 22The role of the hippocampus in learning and memory 24Objective of the present thesis 25Chapter 2: A series of pilot studies to determine the threshold for behaviourally sub threshold stroke, seizures and stress 28Abstract 29Experiment la: The effect of a chronic variable stress schedule on performance of the water maze task 32 Materials and Methods 33Results 36Experiment lb: The effects of a variable restraint stress procedure on levels of blood borne CORT 39 Materials and Methods 39Results 40Discussion 41Experiment 2: T...

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“…2004) and NF‐κB dynamic responses to known oxidative stressors (Edwards et al . 1998; Gu et al . 1998, 2000a, 2000b; Wörtwein et al .…”

Section: Chronic Stress Response Characteristics and Agingmentioning

confidence: 99%

Alzheimer's disease β‐secretase BACE1 is not a neuron‐specific enzyme

Rößner

Lange-Dohna

Zeitschel

et al. 2004

Journal of Neurochemistry

Self Cite

153

102

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The brains of Alzheimer's disease (AD) patients are morphologically characterized by neurofibrillar abnormalities and by parenchymal and cerebrovascular deposits of b-amyloid peptides. The generation of b-amyloid peptides by proteolytical processing of the amyloid precursor protein (APP) requires the enzymatic activity of the b-site APP cleaving enzyme 1 (BACE1). The expression of this enzyme has been localized to the brain, in particular to neurons, indicating that neurons are the major source of b-amyloid peptides in brain. Astrocytes, on the contrary, are known to be important for b-amyloid clearance and degradation, for providing trophic support to neurons, and for forming a protective barrier between b-amyloid deposits and neurons. However, under certain conditions related to chronic stress, the role of astrocytes may not be beneficial. Here we present evidence demonstrating that astrocytes are an alternative source of BACE1 and therefore may contribute to b-amyloid plaque formation. While resting astroyctes in brain do not express BACE1 at detectable levels, cultured astrocytes display BACE1 promoter activity and express BACE1 mRNA and enzymatically active BACE1 protein. Additionally, in animal models of chronic gliosis and in brains of AD patients, there is BACE1 expression in reactive astrocytes. This would suggest that the mechanism for astrocyte activation plays a role in the development of AD and that therapeutic strategies that target astrocyte activation in brain may be beneficial for the treatment of AD. Also, there are differences in responses to chronic versus acute stress, suggesting that one consequence of chronic stress is an incremental shift to different phenotypic cellular states.

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Responses in the aged rat brain after total immunolesion

Cited by 26 publications

References 49 publications

Sympathetic Sprouting Drives Hippocampal Cholinergic Reinnervation That Prevents Loss of a Muscarinic Receptor-Dependent Long-Term Depression at CA3–CA1 Synapses

Sympathetic Sprouting Drives Hippocampal Cholinergic Reinnervation That Prevents Loss of a Muscarinic Receptor-Dependent Long-Term Depression at CA3–CA1 Synapses

Revisiting the cholinergic hypothesis in the development of Alzheimer's disease

Alzheimer's disease β‐secretase BACE1 is not a neuron‐specific enzyme

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