Fall in density, but not number of myenteric neurons and circular muscle nerve fibres in guinea‐pig colon with ageing

Abstract

In guinea-pig ileum, ageing has been associated with a decrease in enteric neurons. This study examined guinea-pig colon and measured changes in gut dimensions, neuron size, density and ganglionic area. Changes in motor nerve fibres in the circular muscle were also measured. Myenteric neurons in whole-mount preparations of mid-colon from 2-week, 6-month, and 2-year-old guinea-pigs were labelled immunohistochemically with the neuronal marker human neuronal protein HuC/HuD, and numbers of neurons mm(-2), neuronal size, ganglionic area mm(-2), gut length, circumference and muscle thickness were measured. Corrected numbers of neurons mm(-2) and ganglionic area mm(-2) accounting for growth of the colon were calculated. Additionally, nerve fibres in circular muscle cross-sections were labelled with antibodies against nitric oxide synthase (NOS) and substance P (SP) and the density of nerve fibres in circular muscle was measured. The numbers of neurons mm(-2) decreased by 56% (from 2 weeks to 2 years) with no change in neuron size. Total neuron numbers decreased by 19% (P = 0.14) when adjusted for changes in length and circumference with age. The percentage area of NOS- and SP-immunoreactive (IR) nerve fibres in the circular muscle decreased (P< 0.001), but the total area of NOS and SP-IR nerve fibres increased (P < 0.01) due to an age-related increase in muscle thickness. The density of myenteric neurons in guinea-pig mid-colon halved from 2 weeks to 2 years, but when the increase in colon dimensions was considered, the number of neurons decreased by only 19%. The percentage area of motor nerve fibres in the circular muscle decreased with no change in total volume of nerve fibres.

The effects of quercetin on liver regeneration after liver resection in rats

“…Similar results were observed in the guinea pig small intestine [13], the stomach of sheep [26], and a mouse [9]. However, some recent research has shown that there is no significant loss in the number of neurons in the myenteric plexus associated with aging [14,24,36]. We assume that the reasons for these differences may be due to technical difficulties in the precise counting of the number of neurons.…”

“…These studies were carried out in a number of animal species [27,29,31]. The literature that has been documented support varying data from those which indicate the significant reduction (30-50%) in the number of neurons [17,33] to those where there is no significant loss of the neurons [14,24,36] in the aging process. There are a number of studies [7,34] which describe changes in ENS due to the introduction of certain dietary restrictions in experimental animals.…”

The Aging Colon: The Role of Enteric Neurodegeneration in Constipation

“…However, others have shown that the expression of neuronal nitric oxide synthase (nNOS) is differentially affected in young and aged rats [7]. Preclinical studies in the guinea pig colon have also shown that aging has been associated with a decrease in neurons in the ENS; however, a fall in density rather than the number of myenteric neurons is thought to be the major change with age [8]. Although data from humans to investigate age-related changes in the colon are limited, recent evidence from human sigmoid colon circular muscle suggests that a decrease in nerve fiber density occurs with growth in response to an increase in circular muscle thickness that occurs during early childhood to adolescence; however, this study found no further changes were observed with aging [9].…”

Chronic constipation: Lessons from animal studies

“…They also show impaired colonic transit and constipation [18]. For example, in the intestine of aged guinea-pigs, there is a reduction of approximately half the number of myenteric neurons in the small intestine, with no reduction in the neuronal cell size [19]. Also, in rats, there is a clear reduction in the number of myenteric neurons, which has been directly associated with a reduction in output of fecal pellets with age [18].…”