Mechanisms Of Memory Loss Research Articles

A novel mechanism of memory loss in Alzheimer\u2019s disease mice via the degeneration of entorhinal\u2013CA1 synapses

The entorhinal cortex (EC) is one of the most vulnerable brain regions that is attacked during the early stage of Alzheimer’s disease (AD). Here, we report that the synaptic terminals of pyramidal neurons in the EC layer II (ECIIPN) directly innervate CA1 parvalbumin (PV) neurons (CA1PV) and are selectively degenerated in AD mice, which exhibit amyloid-β plaques similar to those observed in AD patients. A loss of ECIIPN–CA1PV synapses disables the excitatory and inhibitory balance in the CA1 circuit and impairs spatial learning and memory. Optogenetic activation of ECIIPN using a theta burst paradigm rescues ECIIPN–CA1PV synaptic defects and intercepts the decline in spatial learning and memory. These data reveal a novel mechanism of memory loss in AD mice via the selective degeneration of the ECIIPN–CA1PV pathway.

Naringin Enhances CaMKII Activity and Improves Long-Term Memory in a Mouse Model of Alzheimer’s Disease

The Amyloid-β (Aβ)-induced impairment of hippocampal synaptic plasticity is an underlying mechanism of memory loss in the early stages of Alzheimer’s disease (AD) in human and mouse models. The inhibition of the calcium/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation plays an important role in long-term memory. In this study, we isolated naringin from Pomelo peel (a Citrus species) and studied its effect on long-term memory in the APPswe/PS1dE9 transgenic mouse model of AD. Three-month-old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two naringin (either 50 or 100 mg/kg body weight/day) groups, or an Aricept (2 mg/kg body weight/day) group. After 16 weeks of treatment, we observed that treatment with naringin (100 mg/kg body weight/day) enhanced the autophosphorylation of CaMKII, increased the phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor at a CaMKII-dependent site and improved long-term learning and memory ability. These findings suggest that the increase in CaMKII activity may be one of the mechanisms by which naringin improves long-term cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD.

Neurotrophins Enhance CaMKII Activity and Rescue Amyloid-β-Induced Deficits in Hippocampal Synaptic Plasticity

Amyloid-β (Aβ) peptide-induced impairment of hippocampal synaptic plasticity is considered an underlying mechanism for memory loss in the early stages of Alzheimer's disease and its animal models. We previously reported inhibition of long-term potentiation (LTP) and miniature excitatory postsynaptic currents by oligomeric Aβ(1-42) at hippocampal synapses. While multiple cellular mechanisms could be involved in Aβ-induced synaptic dysfunction, blockade of activity-dependent autophosphorylation of Ca2+ and calmodulin-dependent protein kinase II (CaMKII) appeared to be a major component of Aβ action in our studies. The present study further tested this hypothesis and examined the therapeutic potential of trkB receptor-acting neurotrophins in rescuing Aβ-induced synaptic and signaling impairments. As expected, treatment of rat hippocampal slices with Aβ(1-42) significantly reduced LTP in the Schaffer collateral-CA1 pathway and dentate medial perforant path. LTP-associated CaMKII activation and AMPA receptor phosphorylation were blocked by Aβ(1-42) at the same concentration that inhibited LTP. Aβ-induced LTP impairment, however, was prevented when slices were co-treated with neurotrophin 4 (NT4). Western blotting and immunohistochemical analyses confirmed that treatment with NT4 or brain-derived neurotrophic factor, another trkB-acting neurotrophin, could oppose Aβ action, enhancing autophosphorylation of CaMKII, and AMPA receptor phosphorylation at a CaMKII-dependent site. These findings support the view that CaMKII is a key synaptic target of Aβ toxicity as well as a potential therapeutic site of neurotrophins for Alzheimer's disease.

Mechanisms of memory loss in Aβ and tau mouse models

Although memory loss is the central symptom of Alzheimer's disease, the pathophysiological mechanisms leading to dementia are poorly understood. It is difficult to answer this issue with studies in humans and impossible in cultured cells. Therefore animal models are needed to elucidate the molecular mechanisms leading to dementia. The chief neuropathological changes during Alzheimer's disease, namely neurofibrillary tangles and amyloid plaques, have helped us to determine which molecules to focus upon in the animal models, specifically Abeta (amyloid beta) and tau. This paper presents my perspective on what we have learnt about mechanisms of memory loss from Abeta and tau mouse models of Alzheimer's disease.

Description of isolated macroscopic systems inside quantum mechanics

For an isolated macrosystem classical state parameters ζ( t) are introduced inside a quantum mechanical treatment. By a suitable mathematical representation of the actual preparation procedure in the time interval [ T, t 0] a statistical operator is constructed as a solution of the Liouville—von Neumann equation, exhibiting at time t the state parameters ζ( t′), t 0 ≤ t′ ≤ t, and preparation parameters related to times T ≤ t′ ≤ t 0. Relation with Zubarev's nonequilibrium statistical operator is discussed. A mechanism for memory loss is investigated and time evolution by a semigroup is obtained for a restricted set of relevant observables, slowly varying on a suitable time scale.

Loss of spectral memory in the relaxation oscillations of a multimode solid-state laser.

To test the application of solid-state lasers to intracavity laser absorption spectroscopy (ICLAS), we studied a neodymium-doped glass laser, in the presence of extreme relaxation oscillations (up to ${10}^{8}$ intensity contrast). The contrast of these oscillations could be varied by changing the Q-switch transition time. The recorded absorption spectra accurately follow the regular ICLAS behavior except when the intensity in the first relaxation oscillation minimum becomes too low. In such a case, we find that the ICLAS absorption spectrum accumulated during the first spike is ``forgotten'' by the system. Numerical simulations were done which accurately describe the observed transition to a regime of memory loss, when the number of photons circulating in each mode drops close to 1. These simulations show that the mechanism of memory loss is the prevailing of spontaneous over stimulated emission. This effect sets the fundamental limit of the sensitivity of an ICLAS spectrometer where the nonlinear mode interactions are negligible. This effect was observed before only in a diode laser system with high internal losses. In this paper we report an observation of ICLAS sensitivity saturation by spontaneous emission during relaxation oscillations in a laser with low cavity losses. \textcopyright{} 1996 The American Physical Society.

Memory and attention in patients with senile dementia of the alzheimer type and in normal elderly subjects

Previous studies have shown that cholinergic blockade in normal subjects induces impairment of vigilance as well as memory deficits. In the present investigation we have examined the validity of this pharmacological model of dementia by administering a battery of cognitive tasks to patients with mild and moderate senile dementia of the Alzheimer type and to age-matched controls. In contrast to volunteers receiving scopolamine all the mildly demented patients, and half of those moderately affected, performed normally on tests of vigilance whilst exhibiting the expected memory deficits. These data suggest that the mechanism of memory loss in Alzheimer's disease may differ from that found in scopolamine-induced amnesia.