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Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease.

ABSTRACT: Cognitive deficits occur in over half of multiple sclerosis patients, with hippocampal-dependent learning and memory commonly impaired. Data from in vivo MRI and post-mortem studies in MS indicate that the hippocampus is targeted. However, the relationship between structural pathology and dysfunction of the hippocampus in MS remains unclear. Hippocampal neuropathology also occurs in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. Although estrogen treatment of EAE has been shown to be anti-inflammatory and neuroprotective in the spinal cord, it is unknown if estrogen treatment may prevent hippocampal pathology and dysfunction. In the current study we examined excitatory synaptic transmission during EAE and focused on pathological changes in synaptic protein complexes known to orchestrate functional synaptic transmission in the hippocampus. We then determined if estriol, a candidate hormone treatment, was capable of preventing functional changes in synaptic transmission and corresponding hippocampal synaptic pathology. Electrophysiological studies revealed altered excitatory synaptic transmission and paired-pulse facilitation (PPF) during EAE. Neuropathological experiments demonstrated that there were decreased levels of pre- and post-synaptic proteins in the hippocampus, diffuse loss of myelin staining and atrophy of the pyramidal layers of hippocampal cornu ammonis 1 (CA1). Estriol treatment prevented decreases in excitatory synaptic transmission and lessened the effect of EAE on PPF. In addition, estriol treatment prevented several neuropathological alterations that occurred in the hippocampus during EAE. Cross-modality correlations revealed that deficits in excitatory synaptic transmission were significantly correlated with reductions in trans-synaptic protein binding partners known to modulate excitatory synaptic transmission. To our knowledge, this is the first report describing a functional correlate to hippocampal neuropathology in any MS model. Furthermore, a treatment was identified that prevented both deficits in synaptic function and hippocampal neuropathology.

SUBMITTER: Ziehn MO

PROVIDER: S-EPMC4343001 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease.

Ziehn Marina O MO Avedisian Andrea A AA Dervin Shannon M SM O'Dell Thomas J TJ Voskuhl Rhonda R RR

Laboratory investigation; a journal of technical methods and pathology 20120423 8

Cognitive deficits occur in over half of multiple sclerosis patients, with hippocampal-dependent learning and memory commonly impaired. Data from in vivo MRI and post-mortem studies in MS indicate that the hippocampus is targeted. However, the relationship between structural pathology and dysfunction of the hippocampus in MS remains unclear. Hippocampal neuropathology also occurs in experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. Although estrogen trea ...[more]

PMID: 22525427

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Project description:Functional diversification along the longitudinal axis of the hippocampus is a rapidly growing concept. Modulation of synaptic transmission by neurotransmitter receptors may importantly contribute to specialization of local intrinsic network function along the hippocampus. In the present study, using transverse slices from the dorsal and the ventral hippocampus of adult rats and recordings of evoked field postsynaptic excitatory potentials (fEPSPs) from the CA1 stratum radiatum, we aimed to compare modulation of synaptic transmission between the dorsal and the ventral hippocampus. We found that transient heterosynaptic depression (tHSD, <2 s), a physiologically relevant phenomenon of regulation of excitatory synaptic transmission induced by paired stimulation of two independent inputs to stratum radiatum of CA1 field, has an increased magnitude and duration in the ventral hippocampus, presumably contributing to increased input segregation in this segment of the hippocampus. GABAB receptors, GABAA receptors, adenosine A1 receptors and L-type voltage-gated calcium channels appear to contribute differently to tHSD in the two hippocampal segments; GABABRs play a predominant role in the ventral hippocampus while both GABABRs and A1Rs play important roles in the dorsal hippocampus. Activation of GABAB receptors by an exogenous agonist, baclofen, robustly and reversibly modulated both the initial fast and the late slow components of excitatory synaptic transmission, expressed by the fEPSPslope and fEPSP decay time constant (fEPSP?), respectively. Specifically, baclofen suppressed fEPSP slope more in the ventral than in the dorsal hippocampus and enhanced fEPSP? more in the dorsal than in the ventral hippocampus. Also, baclofen enhanced paired-pulse facilitation in the two hippocampal segments similarly. Blockade of GABAB receptors did not affect basal paired-pulse facilitation in either hippocampal segment. We propose that the revealed dorsal-ventral differences in modulation of synaptic transmission may provide a means for specialization of information processing in the local neuronal circuits, thereby significantly contributing to diversifying neuronal network functioning along the dorsal-ventral axis of hippocampus.

Dataset Information

Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease.

Publications

Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease.

Similar Datasets

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