Medication for Loss of Smell
Library: MED
Keywords: SMELL NOSE OLFACTORY ELDERLY NEURONS
Description: Age has a significant impact on the ability to smell with an estimated 25 percent of the elderly population experiencing some degree of olfactory loss. Other major causes of smell loss include trauma and disease (such as sinusitis). A new study indicates that all three causes of smell loss are associated with the apoptotic death of olfactory sensory neurons in the nose. (Meeting: Triological Society)



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Study Provides Research Essential to Development of Medication for Loss of Smell

More evidence that apoptotic pathway responsible for loss of olfactory sensory neurons, responsible for ability to smell.

Nashville, TN -- Age has a significant impact on the ability to smell with an estimated 25 percent of the elderly population experiencing some degree of olfactory loss. Other major causes of smell loss include trauma and disease (such as sinusitis). A new study indicates that all three causes of smell loss are associated with the apoptotic death of olfactory sensory neurons in the nose.

For mammals to maintain normal ability to smell, the olfactory sensory neurons (OSN) must remain in a balanced state. OSN are quite vulnerable as they are directly exposed to external environmental factors through the nasal mucosa. When lost as a result of normal life experience, OSNs are regenerated to maintain olfactory neuronal homeostasis, or a balance that allows for the continuation of olfactory sensation.

The ability to smell can be compromised by trauma, aging, or sinusitis, all of which cause cell death. There are two types of cell death: apoptosis, death of the cell programmed by enzymes within the cell (caspase-3); or necrosis, death of the cell in response to an external factor. Apoptosis, which can be identified by the presence of enzyme caspase-3, is the common process for removal of aged or damaged cells, cancerous cells, and organ homeostasis. Recently studies have indicated that apoptosis is also employed as a response to injury.

A team of researchers has assessed cell death related to three common but quite distinct causes of clinical olfactory dysfunction: trauma, aging, and sinusitis. They have found that common pathway may facilitate olfactory sensory neuron cell death through aging, trauma, and sinusitis. Robert. C. Kern MD, D. B. Conley, MD, G. K. Haines III, MD, and A. M. Robinson, MD, authors of the study, "Pathology of the Olfactory Mucosa: Implications for the Treatment of Olfactory Dysfunction," will present their findings at the annual meeting of the Triological Society http://www.triological.com/default.htm to be held May 4-6, 2003, at the Gaylord Opryland Hotel, Nashville, TN.

Methodology: To determine the cellular activity involved in olfactory dysfunction, normal and diseased human and animal olfactory mucosa was assessed for immunohistochemical (caspase-3) evidence of apoptosis through aging, trauma, and sinusitis. Examination of olfactory mucosa affected by trauma and aging was accomplished through tissue from C57BL6 mice (aged 12 weeks) and BNxF111 rats (aged 12 weeks and 33 months) obtained by dissection after humanely induced trauma and aging. Analysis of olfactory mucosa affected by sinusitis involved archival human olfactory biopsy tissue obtained from three groups of patients Group1: Three patients with no history of nasal or sinus disease and a normal sense of smell, Group 2: Three patients with sinusitis and a normal sense of smell, and Group 3: Eight patients with sinusitis and an abnormal sense of smell. All tissue samples were examined for evidence of cell apoptosis.

Results: Trauma-affected tissue samples of mice revealed massive caspase-3 activity indicating increased apoptosis. Tissue samples of rats affected by aging revealed an increase in caspase-3 activity (indicating increased apoptosis) in the aged samples, and a low level of caspase-3 in young samples.

In analysis of human tissue samples, caspase-3 activity increased incrementally from very little in Group 1 to more pervasive in Group 2 and even more severe in Group 3.

These finding suggest that apoptosis, or programmed cell death, demonstrated by caspase-3 enzyme activation, is a significant component of olfactory sensory neuron loss in three different pathological settings. The presence of caspase-3 activity signals that the cell is undergoing a process leading to its death.

Conclusion: The determination that a common pathway may mediate olfactory sensory neuron (OSN) cell death from a diverse set of pathologic insults including aging, trauma, and sinusitis offers promise . for the development of drugs for treatment of clinical olfactory dysfunction. Additionally, interference with this pathway of cell death is currently the subject of intense pharmaco-therapeutic research for the management of stroke and meningitis.

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