Size and Degeneration Increase in Herring Bodies During Aging in Hamsters

Histol Histopathol (1 999) 14: 1093-1099 Histology and http://www.ehu.es/histol-histopathol Histopathology Size and degeneration increase in herring bodies during aging in hamsters A. Navarro, J. Tolivia and M. Alvarez-Uría Department of Morphology and Cell Biology, Faculty of Biology and Medicine, University of Oviedo, Oviedo, Spain Summary. The hypothalamo-neurohypophysial tract of Type 111, is distingued by an extensive network of young, adult and aged male hamsters was studied at smooth endoplasmic reticulum (SER), mitochondria and lateral and ventral regions of hypothalamus by means of a few NGVs. These authors hypothesized that type 1 electron microscopy. Neurosecretory swelling axons Herring bodies serve as temporary storage site for (Herring bodies) were usually found as classically NGVs. If arrest is of longer periods, autophagic events described containing abundant neurosecretory granules, are initiated, causing the characteristic appearance of mitochondria, few microtubules and profiles of smooth Type 11 Herring Bodies. Type 111 are considered to endoplasmic reticulum in al1 groups of age. However, in represent the beginning of return to a normal stage. aged hamsters, starting at 18-month-old subjects, we The HNS has been implicated in the diminished observed that the size of some neurosecretory axons was capacity to maintain water balance and the ability to highly increased. Autophagic and degenerative features respond to a salt-loading stimulus during aging (Sladek were seen in the larger ones. These data could suggest et al., 1981; Phillips et al., 1984; Goudsmit et al., 1988). abnormal axonal storage or axonal transport blocked Severa1 possible hypotheses could solve this question: 1) during aging. The implications in the role of hypo- a decrease in the biosynthesis of neuropeptides; 2) thalamus-neurohypophysial system during aging are reduction in the axonal transport of these peptides; 3) discussed. decrease in the ability of the neurohypophysis to release hormones; and 4) decrease in kidney function. On the Key words: Aging, Electron microscopy, Axonal one hand, the literature states that changes during aging transport, Hypothalamus in the HNS produce a decrease in neurosecretory activity (Dorsa and Bottemiller, 1982; Calzá et al., 1990). However, no significant cell loss was shown in these lntroduction nuclei during aging that could explain this suggested decreased secretory activity of HNS (Hsü and Peng, The transport of neurosecretory material of the 1978; Peng and Hsü, 1982; Sartin and Lamperti, 1985; hypothalamo-neurohypophysial system (HNS) occurs Goudsmit et al., 1990). On the other hand, the neuro- into large axons of magnocellular peptidergic neurons peptide production by these nuclei has been reported between the perikaryon origin and its ending in the unaltered or increased in old subjects (Fliers and Swaab, neural lobe (for review see Kupfermann, 1991). The 1983; Davies et al., 1985; Silverman and Sladek, 1991; axons form three compartments: undilated axons; Lucassen et al., 1993; Navarro et al., 1997). The cause preterminal dilated "nerve swellings" (Herring bodies) for the activation of neurons is as yet unknown, but a and terminal "nerve endings" in the median eminence possible explanation is the loss of vasopressin binding and neurohypophysis, according to Morris' sites in the kidney with aging (Ravid et al., 1985; nomenclature (1976). These Herring bodies were Davies, 1987). The apparently divergent data in the classified into another three types (Dellmann and synthesis, the storage and the neurohormone release may Rodriguez, 1970; Polenov and Garlov, 1971): Type 1, be the result of a reduction in axonal transport with age. characterized by numerous neurosecretory granulated In this respect, a significant difference of transport of vesicles (NGVs); Type 11, with many autophagic newly synthesized neurohormones in young and old vacuoles, dense bodies, NGVs and empty vesicles; and mice exists (Fotheringhan et al., 1991). We intended to work on this hypothesis by ultra- Offprint requests to: Dr. Ana Navarro, Departamento de Morfología y structural study and quantitative methods, the hypo- Biología Celular, Facultad de Biología y Medicina, Universidad de thalamo-neurohypophysial tract in hamsters during the Oviedo, Julián Clavería s/n, Oviedo 33006. Spain. Fax: 348-5103618. lifetime. The observations of fine structural changes in e-mail: [email protected] these large axons between young and old hamsters are Herring bodies in aging hamsters described and discussed in the present paper. size of the axons probably depending of synthesis or secretory cycles. Measurernents of Herring bodies Materials and methods usually varied from 20 to 200 prn2 in transectional area in young harnsters. Most of these large swellings were Experimental animals unmyelinizated axons, although occasionally they were surrounded by rnyelin layer. The normal Herring bodies, Male Syrian harnsters (Mesocricetus auratus) frorn usually found contained abundant neurosecretory our closed colony established in the Morphology and granules (NSGs), rnitochondria, few rnicrotubules and Cellular Biology Departrnent, Oviedo University, in profiles of srnooth endoplasrnic reticulurn in al1 age 1985, were ernployed in the present study. Animal groups. groups of 3, 6, 12, 18, 24 and 30 rnonths of age were However, already in the 18-rnonth-old harnsters, studied. Five specirnens were used for each age, larger dilated neurosecretory axons appeared in the cornprising a total of 30 hamsters. Since the average life ventral surface of the hypothalarnus, rnost of thern just span for our golden harnster is 1.6 years, our three oldest lateral to the rostral part of the median erninence. As groups are considered aged. They were housed in a seen with light rnicroscopy, these dilated axons could be ternperature-controlled roorn (2022 "C)with photoperiod identified at the electron rnicroscopic leve1 as huge of 14:lOh lightldark cycles and with free access to Herring bodies. The average cross-sectional area of these laboratory chow and water. Any anirnals with any Herring bodies was 407191.14 prn2. evidence of rnacroscopic pathology (detected by a An irregular profile against the round or oval profile detailed autopsy carried out during the perfusion of normal Herring bodies was another cornrnon process) were excluded frorn the study. characteristic of these huge neurosecretory axons (Figs. 1, 2). The axonal plasrnalernrna presented deep Tissue treatment invaginations, sornetirnes with small processes (Fig. 3A,B). In addition, the presence of normal Herring Before sacrifice, animals were anaesthetized with bodies surrounding or in direct apposition with the huge sodiurn pentobarbital (10.5 mg/100 g body weight) and neurosecretory processes, norrnally appeared (Figs. 1,2). transcardially perfused with 4% glutaraldehyde and The dilated processes contained a large accumulation of IrnM CaClz in 0.05M cacodylate buffer at pH 7.3. After neurosecretory granules with different size and density. perfusion brains were removed and fixed in the sarne The nurnber of autophagic vacuoles, dense bodies, dense fixative for 18 hours at 4 "C. The hypothalarnic area was larnellar bodies and swelling rnitochondria was higher dissected out and the tissue blocks were postfixed in a than normal (Fig. 3D). No abnorrnal proliferation of the solution of 1% osrnium tetroxide and 2% potassium srnooth endoplasrnic reticulurn or filarnentous ferrocyanide in 0.05M cacodylate buffer (pH 7.3) for 1 accurnulations was observed. hour, dehydrated in a graded series of acetone and These huge Herring bodies that we have found in ernbedded in Durkupan-ACM (Fluka). Sernithin aged harnsters presented a higher or lower grade of sections, about 0.5 pm thick, were obtained and stained degeneration. Different pattems of degeneration could be with the first step of Tolivia et al. (1994) method. seen between peripheral and central areas (Fig. 2). Ultrathin sections (70-90 nm) were obtained on an Central areas presented more degenerated organelles LKB ultrarnicrotorne and were placed on 300-mesh than peripheral areas, where NSGs formed conserved copper grids with apertures measuring 61x61. They were aggregations (Fig. 3C,D). contrasted with uranyl acetate and lead citrate, and No macrophage or rnicroglial reaction could be seen examined with a Zeiss EM 109. in the nearby neuropil. A normal relationship between For the quantitative study in electron rnicroscopy, a axolernrna and the apposing astroglial rnernbrane was total of three sections were taken for each subject (no seen (Fig. 2). less than 100 prn apart to prevent analysis of profiles of The axonal transectional area presented an a e the sarne axon). Three randomly selected areas of variation. The Herring bodies of srnall size (e200 prngL ) parenchyma in each ultrathin section were selected and are the rnost abundant and constituted 89% of the total scanned at ~3,000.Herring bodies were photographed in axonal profile rneasured under the age of 12 months. cross-sectional orientation and only profiles of axons Medium sized axons (200-400 prn2) represented more with a complete outline were study. Data were expressed than 40% in thel2-18-month-old groups. The giant as mean 2 S.D (Standard deviation). axons (>400 prn2) only appeared in the 18-month-old groups and could represent 20% of axons rneasured (Fig. Results 4). Prorninent swelling (Herring bodies) and undilated Discussion neurosecretory axons could be observed in the lateral and

Load more