Neuroprotective and cognitive enhancing effects of a multi-targeted food intervention in an animal model of neurodegeneration and depression

Neuropharmacology. 2014 Apr:79:738-49. doi: 10.1016/j.neuropharm.2013.11.009. Epub 2013 Nov 25.


Rising neurodegenerative and depressive disease prevalence combined with the lack of effective pharmaceutical treatments and dangerous side effects, has created an urgent need for the development of effective therapies. Considering that these disorders are multifactorial in origin, treatments designed to interfere at different mechanistic levels may be more effective than the traditional single-targeted pharmacological concepts. To that end, an experimental diet composed of zinc, melatonin, curcumin, piperine, eicosapentaenoic acid (EPA, 20:5, n-3), docosahexaenoic acid (DHA, 22:6, n-3), uridine, and choline was formulated. This diet was tested on the olfactory bulbectomized rat (OBX), an established animal model of depression and cognitive decline. The ingredients of the diet have been individually shown to attenuate glutamate excitoxicity, exert potent anti-oxidant/anti-inflammatory properties, and improve synaptogenesis; processes that all have been implicated in neurodegenerative diseases and in the cognitive deficits following OBX in rodents. Dietary treatment started 2 weeks before OBX surgery, continuing for 6 weeks in total. The diet attenuated OBX-induced cognitive and behavioral deficits, except long-term spatial memory. Ameliorating effects of the diet extended to the control animals. Furthermore, the experimental diet reduced hippocampal atrophy and decreased the peripheral immune activation in the OBX rats. The ameliorating effects of the diet on the OBX-induced changes were comparable to those of the NMDA receptor antagonist, memantine, a drug used for the management of Alzheimer's disease. This proof-of-concept study suggests that a diet, which simultaneously targets multiple disease etiologies, can prevent/impede the development of a neurodegenerative and depressive disorders and the concomitant cognitive deficits.

Keywords: Anosmia; Cognition; Depression; Dietary intervention; Hippocampus; Inflammation; Memantine; Neurodegeneration; Neuroprotection; Olfactory bulbectomy.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Atrophy / diet therapy
  • Atrophy / drug therapy
  • Atrophy / pathology
  • Atrophy / physiopathology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cognition Disorders / diet therapy*
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / pathology
  • Cognition Disorders / physiopathology
  • Depressive Disorder
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Male
  • Memantine / therapeutic use*
  • Memory Disorders / diet therapy
  • Memory Disorders / drug therapy
  • Memory Disorders / pathology
  • Memory Disorders / physiopathology
  • Neurodegenerative Diseases / diet therapy*
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / physiopathology
  • Neuroimmunomodulation / drug effects
  • Neuroimmunomodulation / physiology
  • Neuroprotective Agents / therapeutic use
  • Nootropic Agents / therapeutic use*
  • Olfaction Disorders / pathology
  • Olfaction Disorders / physiopathology
  • Olfactory Bulb / physiopathology
  • Psychomotor Agitation / diet therapy
  • Psychomotor Agitation / drug therapy
  • Psychomotor Agitation / pathology
  • Psychomotor Agitation / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Space Perception / drug effects
  • Space Perception / physiology
  • Zinc Sulfate


  • Neuroprotective Agents
  • Nootropic Agents
  • Zinc Sulfate
  • Memantine