Research Article Details
| Article ID: | A12664 |
| PMID: | 30338761 |
| Source: | Gen Physiol Biophys |
| Title: | Effect of metabolic syndrome on neural plasticity and morphology of the hippocampus: correlations of neurological deficits with physiological status of the rat. |
| Abstract: | Fat-rich diet (FRD) triggers health complications like hypertension, dyslipidemia, hyperglycemia, insulin resistance and non-alcoholic fatty liver disease, known as the risk factors of metabolic syndrome (MetS), which may result in neurological deficits. The impact of MetS on neuronal functions and brain morphology are poorly understood. We induced MetS-like conditions by exposing hypertriacylglycerolemic (HTG) rats to FRD for eight weeks with the aim to study possible neurological dysfunctions. HTG-FRD rats were compared to HTG rats and Wistar rats on standard diet. The physiological status of the animals was monitored by body, liver and kidney weight. Morphology of the liver, vessel wall and hippocampus were investigated. Basal neurotransmission and synaptic plasticity were measured in the hippocampus ex-vivo. A marked increase of liver weight with marks of steatosis was found in the HTG-FRD group. FRD induced an increase of aortic intima-media thickness. Extracellular recording revealed FRD-induced impairment of long-term potentiation (LTP) at Cornu Ammonis (CA)3-CA1 synapse, contrary to increased presynaptic fiber volley (pV). Reduced thickness of pyramidal cell layer at the CA1 area was found morphometrically. LTP was directly associated with kidney weight and inversely associated with liver weight, pV directly correlated with liver weight, liver/body wt ratio and aortic intima-media thickness. Our results suggest correlations between altered physiological status due to MetS-like conditions and neurological deficits, which may be related with consecutive development of so-called metabolic cognitive syndrome. |
| DOI: | 10.4149/gpb_2018016 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I12 | 10763 | Hypertension | An artery disease characterized by chronic elevated blood pressure in the arteries. https://en.wikipedia.org/wiki/Hypertension, https://www.ncbi.nlm.nih.gov/pubmed/24352797 | disease of anatomical entity/ cardiovascular system disease/vascular disease/ artery disease | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D018 | Aspirin | Chemical drug | DB00945 | AKR1C1 inhibitor; PCNA downregulator | Enhance lipid metabolism | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |